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Appl. cancer res ; 40(6): [1-9], 03 june 2020. ilus, tab
Article in English | LILACS (Americas) | ID: biblio-1103972


Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1

Humans , Female , Ovarian Neoplasms , Cyclin-Dependent Kinase Inhibitor p27 , Carcinoma, Ovarian Epithelial , Immunohistochemistry , Neoadjuvant Therapy , Real-Time Polymerase Chain Reaction
Article in English | WPRIM (Western Pacific) | ID: wprim-811220


OBJECTIVE: Neoadjuvant chemotherapy (NACT) for the treatment of epithelial ovarian cancer (EOC) has remained controversial. This meta-analysis was performed to systematically assess the efficacy and safety of NACT versus primary debulking surgery (PDS) in patients with EOC.METHODS: PubMed, Embase,, and Cochrane Library were queried to assess the therapeutic value of NACT versus PDS in EOC. Electronic databases were queried by using the keywords “ovarian cancer/neoplasms”, “primary debulking surgery”, and “neoadjuvant chemotherapy”.RESULTS: The available trials were pooled, and hazard ratios (HRs), relative risk ratios (RRs) and associated 95% confidence intervals (95% CIs) were determined. Sixteen trials involving 57,450 participants with EOC (NACT, 9,475; PDS, 47,975) were evaluated. We found that NACT resulted in markedly decreased overall survival than PDS in patients with EOC (HR=1.30; 95% CI=1.13–1.49; heterogeneity: p<0.001, ²=82.7%). Furthermore, our results demonstrated that the NACT group displayed increased completeness of debulking removal (RR=1.69, 95% CI=1.32–2.17; heterogeneity: p<0.001, ²=81.9%), and reduced risk of postsurgical death (RR=0.18, 95% CI=0.06–0.51; heterogeneity: p=0.698, ²=0%) and major infection (RR=0.29, 95% CI=0.17–0.51; heterogeneity: p=0.777, ²=0%) compared with patients administered PDS.CONCLUSIONS: This meta-analysis indicated that NACT results in increased completeness of debulking removal, and reduced risk of postsurgical death and major infection compared with PDS, while PDS is associated with improved survival in comparison with NACT in EOC patients.TRIAL REGISTRATION: PROSPERO Identifier: CRD42019120625

Cytoreduction Surgical Procedures , Drug Therapy , Humans , Neoadjuvant Therapy , Odds Ratio , Ovarian Neoplasms , Population Characteristics
Article in English | WPRIM (Western Pacific) | ID: wprim-811212


OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.

Carboplatin , Disease-Free Survival , Drug Therapy , Humans , Neoadjuvant Therapy , Neutropenia , Ovarian Neoplasms , Paclitaxel , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
Article in English | WPRIM (Western Pacific) | ID: wprim-782091


OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) confers similar outcomes as primary debulking surgery and chemotherapy. Little is known about patients who receive NACT but do not undergo debulking surgery. Our aim was to characterize these patients.METHODS: We prospectively identified patients with newly diagnosed stage III/IV ovarian cancer treated with NACT from 7/1/15–12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis.RESULTS: Of 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66–6.72; p<0.001), after adjustment for age, CCI, and dose reductions.CONCLUSIONS: A significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.

Aged , Comorbidity , Cytoreduction Surgical Procedures , Diagnosis , Drug Therapy , Female , Follow-Up Studies , Humans , Methods , Neoadjuvant Therapy , Ovarian Neoplasms , Patient Preference , Proportional Hazards Models , Prospective Studies
Article in English | WPRIM (Western Pacific) | ID: wprim-811197


PURPOSE: Tau is a microtubule-associated protein that can be found in both normal and abnormal breast cells. Whether the expression of Tau protein can predict the response to neoadjuvant chemotherapy (NACT) is still unclear. In this study, we assessed the role of Tau protein expression in predicting a pathological complete response (pCR) to NACT for different subtypes of breast cancer.METHODS: Four hundred and sixty-eight eligible patients were retrospectively recruited in our study. The relationship between clinicopathologic factors, including Tau protein expression, and pCR in different subtypes was evaluated using logistic regression analysis. Correlation between Tau and disease-free survival (DFS) and overall survival (OS) was performed using Kaplan–Meier analysis.RESULTS: The expression of Tau protein was negatively correlated with pCR, especially in triple-negative breast cancer (TNBC). No significant difference was observed in the luminal human epidermal growth factor receptor-2 (HER2)-negative subtype and HER2-positive subtype. Patients with pCR were associated with better DFS and OS (p < 0.05). However, Tau protein expression had no association with either DFS or OS (p > 0.05).CONCLUSION: Tau protein expression can predict pCR before NACT in TNBC, but there was no correlation between Tau expression and DFS or OS.

Breast Neoplasms , Breast , Disease-Free Survival , Drug Therapy , Epidermal Growth Factor , Humans , Logistic Models , Neoadjuvant Therapy , Phenobarbital , Polymerase Chain Reaction , Retrospective Studies , tau Proteins , Triple Negative Breast Neoplasms
Article in English | WPRIM (Western Pacific) | ID: wprim-811196


PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system.METHODS: Of the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria.RESULTS: In both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001).CONCLUSIONS: Staging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.

Breast Neoplasms , Breast , Humans , Joints , Neoadjuvant Therapy , Prognosis
São Paulo; s.n; 2020. 75 p. figuras, tabelas.
Thesis in Portuguese | LILACS (Americas), Inca | ID: biblio-1102483


Introdução: A incidência e o impacto preditivo e prognóstico da expressão de PD-L1 por imunoistoquimica em pacientes com câncer gástrico submetidos a tratamento perioperatório é incerto. Também não há dados concretos sobre o efeito da quimioterapia neoadjuvante sobre esta expressão. Nesta coorte objetivamos determinar a expressão de PD-L1 pelo Combined Positive Score (CPS) em amostras de biópsias de neoplasias gástricas pré-neoadjuvância e em peças cirúrgicas após este tratamento e correlacionar estes achados com a resposta à quimioterapia pré-operatória e com os resultados de sobrevida observados. Método: Esta é uma coorte retrospectiva de pacientes com câncer gástrico e de transição gastro-esofágica que receberam tratamento neoadjuvante e cirurgia com intuito curativo no A.C.Camargo Cancer Center de 2007 a 2017. Pacientes submetidos à esofagectomia como procedimento principal, com tumores de coto gástrico e com histologias mistas foram excluídos. Dados clínicos foram coletados dos prontuários e de banco de dados prospectivo mantido pelo Núcleo de Cirurgia Abdominal. Amostras da biópsia pré tratamento e de áreas representativas da neoplasia colhidas das peças cirúrgicas após a neoadjuvância e representadas em TMA foram analisadas por IHQ utilizando-se o anticorpo 22C3 PharmDx da DAKO com os resultados analisados pelo CPS. A sobrevida global e livre de doença foram calculadas pelo método de Kaplan-Meier e a regressão de Cox foi usada para calcular os HR crus e ajustados para fatores prognósticos. Resultado: Duzentos e setenta pacientes foram incluídos, com mediana de idade de 58,9 anos, 51,5% estadiados como cT3-T4N+, 45% com histologia difusa, sendo que 87,8% completaram o tratamento neoadjuvante. A análise patológica pós-neoadjuvância revelou 13% de casos com resposta completa e 53% com regressão tumoral inferior a 50%. Com um seguimento mediano de 60,3 meses, as sobrevidas global e livre de doença medianas não foram atingidas. O porcentual de casos PD-L1 positivos nas biópsias foi 11,4% e em peças cirúrgicas foi 18,6% com CPS mediano de 3 (IQR 2,0 ­ 7,5) e 9 (IQR 5,0 ­ 20,0) respectivamente. Em 18,9% dos casos com amostras pareadas, as mesmas foram classificadas como PD-L1 negativas nas biópsias e positivas na peça cirúrgica pós-neoadjuvância. A expressão proteica do PD-L1 não esteve associada nem à resposta patológica nem aos resultados de sobrevida. Conclusão: A expressão proteica de PD-L1 em pacientes com câncer gástrico e de TEG submetido à quimioterapia perioperatória é baixa e significativamente diferente quando analisada nas biópsias pré-tratamento e nas peças cirúrgicas. Em nossa casuística, esta expressão não apresentou impacto na resposta patológica e nos resultados de sobrevida observados (AU)

Background. The incidence, prognostic and predictive impacts of PD-L1 IHC expression in locally advanced gastric cancer is uncertain as well as the effect of preoperative treatment on this expression. We aimed to determine the expression of PD-L1 by CPS in the pre-treatment biopsy and surgical specimens of patients with gastric cancer who received neoadjuvant therapy and its association with pathological response and survival outcomes. Method. Retrospective cohort of patients treated at a cancer center from 2007 to 2017. Patients with confirmed gastric or GEJ adenocarcinoma who received neoadjuvant treatment and curative-intent surgery were included. Gastric stump tumors and those who had a total esophagectomy were excluded. Clinical data were obtained from medical charts. Biopsy samples and a tissue microarray with the most representative areas of the surgical specimen were used to evaluate PD-L1 IHC expression with 22C3 phamDx antibody. Results were analyzed using the CPS score. Overall and DFS survival included the Kaplan-Meier product-limit estimator and a Cox regression was used to obtain crude and adjusted HR for prognostic factors. Results. 270 patients were included: median age was 58.9 years, most (51.5%) had cT3-T4N+ stages, 45% had diffuse histology and 87.8% completed the preoperative regimen. 13% had a pCR, while 53% had minimal tumor regression. With a median follow-up of 60.3 months (CI 95% 54.7 ­ 65.8), the median OS and DFS were not reached. 11.4% of biopsies and 18.6% of surgical specimens had positive CPS, with a median score of 3 (IQR 2,0 ­ 7,5) and 9 (IQR 5.0 ­ 20.0) respectively. In 18.9% of paired samples the PD-L1 expression was found to be negative in the biopsy sample and positive in the surgical specimen. PD-L1 expression was neither associated with pathologic response after neoadjuvant chemotherapy, nor with survival outcomes. Conclusion. PD-L1 expression on the setting of locally advanced gastric cancer was low and it was different when biopsy and surgical specimens were compared. No impact on survival results could be detected.

Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Prognosis , Stomach Neoplasms , Immunohistochemistry , Retrospective Studies , Neoadjuvant Therapy
Autops. Case Rep ; 9(4): e2019116, Oct.-Dec. 2019. ilus
Article in English | LILACS (Americas) | ID: biblio-1024253


Basal cell carcinoma (BCC) is the most common skin cancer. It generally has an indolent course with low rates of metastasis and mortality. However, BCC is locally invasive and can cause significant morbidity due to destructive local spread. We report our experience with a patient who was referred to our skin cancer unit due to a previously neglected lesion on the parietal region of the scalp, which had developed for 7 years. The patient was prescribed vismodegib on the basis that surgery could cause excessive functional and aesthetic damage. The patient had an objective partial response after 20 months of treatment. He was then submitted to radical skin excision, leaving a large defect that was reconstructed using a free latissimus dorsi muscle flap. The patient recovered well, and at the 1-year follow-up there were no signs of local recurrence. Our case demonstrates the value of vismodegib treatment prior to surgery in a locally advanced, high-risk scalp BCC and highlights the importance of an individualized and specialized approach with these patients, within a multidisciplinary team.

Humans , Male , Middle Aged , Carcinoma, Basal Cell/drug therapy , Head and Neck Neoplasms/pathology , Patient Care Team , Reconstructive Surgical Procedures , Neoadjuvant Therapy , Antineoplastic Agents/therapeutic use
J. coloproctol. (Rio J., Impr.) ; 39(4): 365-372, Oct.-Dec. 2019.
Article in English | LILACS (Americas) | ID: biblio-1056638


Abstract Introduction Colorectal cancer is amongst the most prevailing malignancies in the world and it is associated with a relatively high mortality rate. Rectal cancer occurs in 20-30% of all colorectal cancer cases, and 25% of this present synchronous metastatic disease. This study aims to review the current treatment approaches for rectal cancer patients with synchronous liver metastases, as there are no specific guidelines for the management of this group of patients. Methods A systematic literature search was performed on Pubmed database with a 10 year timeline limitation from 2008 to 2018. Results Currently, the only potentially curative approach remains to be the surgical resection. Conventionally, the classical strategy of these patients involves resection of rectal tumor, followed by liver resection, with chemotherapy sessions between the two procedures. However, recent studies have reported no inferiority, in safety and survival outcomes, when compared with other approaches (liver-first resection or simultaneous resection), except when symptoms of primary tumor are present. Hence, treatment strategy should be individualized based on the assessment of metastatic extent, primary tumor symptoms and the patient's overall clinical status. Chemotherapy and targeted agents have substantially contributed to overall survival improvements, allowing enhanced tumor down staging. Conclusion Complete resection of liver metastases is considered the major condition for a potential survival outcome in these patients. Management of these patients should include a multidisciplinary team with consideration of each individual specificities. Prospective randomized trials are needed to elucidate the optimal treatment strategy.

Introdução: O câncer colorretal está entre as neoplasias mais prevalentes no mundo, apresentando a uma taxa de mortalidade relativamente alta. Ele corresponde a 20% a 30% de todos os casos de câncer colorretal; 25% dos casos apresentam doença metastática síncrona. Este estudo teve como objetivo revisar as abordagens atuais de tratamento para pacientes com câncer retal com metástases hepáticas síncronas, uma vez que não existem diretrizes específicas para o manejo deste grupo de pacientes. Métodos: Uma busca sistemática da literatura foi realizada no banco de dados PubMed com uma limitação temporal de 10 anos (2008 a 2018). Resultados: Atualmente, a ressecção cirúrgica ainda é a única abordagem potencialmente curativa. Tradicionalmente, a estratégia clássica para o tratamento desses pacientes envolve a ressecção do tumor retal, seguida de ressecção hepática, com sessões de quimioterapia entre os dois procedimentos. No entanto, ao comparar a abordagem tradicional com outras técnicas (ressecção em primeiro plano do fígado ou ressecção simultânea), estudos recentes não relataram inferioridade nos desfechos de segurança e sobrevida, exceto quando sintomas de tumor primário estão presentes. Portanto, a estratégia de tratamento deve ser individualizada com base na avaliação da extensão metastática, nos sintomas primários do tumor e no estado clínico geral do paciente. A quimioterapia e os agentes dirigidos contribuíram substancialmente para as melhorias gerais na sobrevida, permitindo uma maior redução do estadiamento tumoral. Conclusão: A ressecção completa de metástases hepáticas é considerado o principal requisito para um possível resultado de sobrevida nesses pacientes. O manejo desses pacientes deve incluir uma equipe multidisciplinar e considerar as características específicas de cada paciente. Estudos prospectivos randomizados são necessários para elucidar a estratégia de tratamento ideal.

Humans , Rectal Neoplasms/surgery , Liver Neoplasms/surgery , Neoplasms, Multiple Primary/surgery , Rectal Neoplasms/pathology , Rectal Neoplasms/drug therapy , Neoadjuvant Therapy , Proctectomy , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Neoplasms, Multiple Primary/drug therapy
Rev. argent. mastología ; 38(138): 14-34, jul 2019. graf
Article in Spanish | LILACS (Americas) | ID: biblio-1116786


Introducción Existe consenso sobre los subgrupos de pacientes con más probabilidades de beneficiarse del tratamiento neoadyuvante, pero su utilización en la práctica clínica es variable. Las pacientes con cáncer de mama en etapa temprana susceptibles de requerir quimioterapia adyuvante podrían considerarse para realizar quimioterapia neoadyuvante (qtna). Objetivos Evaluar las tasas de cirugía conservadora en pacientes con cáncer de mama que reciben qtna y describir las tendencias de respuestas clínica, imagenológica y patológica en la mama y la axila. Material y método Se realizó una evaluación retrospectiva de 125 pacientes con cáncer de mama invasor (Estadios IB-IIA/B-IIIA), operadas en el Instituto Alexander Fleming en el período 2002-2018. Resultados Las tasas más altas de respuesta patológica completa (pcr) se obtuvieron en los tumores her2, tn y Luminal B-her2, representando el 56%, 55% y 40% respectivamente. En la respuesta patológica completa ganglionar, las tasas más altas se obtuvieron en los Luminal B-her2 82%, los tn 80% y los her2 70%. Las tasas de cirugía conservadora fueron: para Luminal A 44%, para Luminal B 58%, para Luminal B-her2 54%, para her2 76% y para tn 59%. Conclusiones Concordante con trabajos publicados, se describen altas tasas de cirugía conservadora y altas tasas de pcr en tumores her2 y tn

Introduction Even though there is evidence about better outcomes after neoadjuvant chemotherapy (nac) for breast cancer (bc), it is unclear who are the indicated patients and what are the correct indications for using it. Our hypothesis is that early stage bc patients, who are identified as susceptible for adjuvant chemotherapy, could be the most benefited of receiving nac. Objectives We aimed to study the number of patients who received nac and breast conserving surgery (bcs) assessing clinical, pathological and radiological response in both, breast and axilla. Materials and method We carried out a retrospective study of 125 patients newly diagnosed of bc (Stage IB-IIA-B and IIIA) who received nat and bcs in our institution, "Instituto Alexander Fleming", during the 2002-2018 period Results We obtained the higher rates of pathological complete response (pcr) in her2 being 56%; for tn was 55% and 40% for Luminal B-her2. The highest rates of complete pathological lymph node response were obtained in Luminal B-her2 82%, tn 80% and her2 70%. The rates for bcs where 44%, 58%, 54% and 76% for Luminal A, Luminal B, Luminal B-her2 and her2 respectively. Conclusions There is current data available supporting our findings, having similar results for bcs and pcr performing bcs after nat

General Surgery , Breast Neoplasms , Chemotherapy, Adjuvant , Neoadjuvant Therapy
Rev. argent. mastología ; 38(138): 55-78, jul 2019. graf
Article in Spanish | LILACS (Americas) | ID: biblio-1116812


El cáncer de mama Triple Negativo ha sido estudiado a lo largo de los años principalmente por ser uno de los de peor pronóstico y, además, por carecer de terapia blanco. El debut de esta patología se puede dar de diversas formas, y es en función de esto que el especialista optará entre distintas medidas: ya sea instaurará tratamiento adyuvante o neoadyuvante o enfrentará directamente la enfermedad metastásica. Si bien muchas veces las terapias a utilizar no se encuentran bien establecidas, las drogas quimioterápicas no difieren de las de los otros subtipos. Pero, al ser tumores que se asocian con mayor frecuencia a mutaciones en el brca, se han investigado tratamientos que apuntan más hacia el defecto de reparación del adn mediante la recombinación homóloga, como son los platinos y los inhibidores del parp. Por otro lado, no se debe dejar de mencionar las terapias dirigidas hacia los distintos subtipos tumorales como, por ejemplo, los antagonistas androgénicos que aún se encuentran en estudio. Sabemos que el cáncer de mama Triple Negativo es una patología extremadamente difícil de tratar, pero todavía quedan en el tintero investigaciones para esclarecer y enfocar las terapias blanco según cada subtipo dentro de estos tumores

Over the years, Triple Negative breast cancers have been studied, mainly because of its poor prognosis but also because it lacks a target therapy. Its debut may occur in different ways, therefore specialists can choose between different measures for treatment. The choices lay between adjuvant or neoadjuvant therapies or to directly face metastatic disease. Although these therapies are not fully established, chemotherapeutic drugs do not differ from other breast cancer subtypes. The association between these tumors and brca mutations is so high, target treatments have been focusing in dna defect repair, through homologous recombination, such as platinum-based chemotherapy and parp inhibitors. Other target therapies should be taken into account, such as androgenic antagonists, which are still being studied. Considering the nature of such an heterogeneous disease, which is extremely difficult to treat, we should acknowledge research in this subject is yet to be clarified to be able to provide new target therapies for each subtype within the triple negative tumors

Therapeutics , Breast Neoplasms , Neoadjuvant Therapy , Drug Therapy , Triple Negative Breast Neoplasms
Rev. argent. coloproctología ; 30(2): 73-74, Jun. 2019. ilus
Article in Spanish | LILACS (Americas) | ID: biblio-1025577


Introducción: El carcinoma verrucoso o tumor de Ackerman es una rara entidad relacionada con la infección por el virus del papiloma humano, comportándose como una variante menos agresiva del carcinoma epidermoide. Caso clínico: Presentamos el caso clínico de un paciente de sexo masculino de 45 años portador de una gran lesión perianal con compromiso del canal anal y el aparato esfinteriano. Discusión: Existen varias alternativas para el tratamiento del tumor de Ackerman. Sin embargo en casos como este, y sobre todo ante la ausencia de respuesta al tratamiento de quimioradioterapia, se requiere de una resección amplia y radical. Pese a ello, la recidiva es frecuente. Conclusiones: En el caso analizado se destaca la forma particularmente agresiva de esta patología, con extensa invasión local y pobre respuesta al tratamiento oncoespecífico inicial.

Introduction: Verrucous carcinoma or Ackerman's tumor is a rare entity related to human papillomavirus infection, behaving as a less aggressive variant of squamous cell carcinoma. Clinical case: We present the case of a 45-year-old male patient with a large perianal lesion with involvement of the anal canal and sphincter. Discussion: Ackerman tumor treatment admits different therapeutic modalities; however, in cases such as this, and especially in the absence of response to chemo-radiotherapy treatment, a broad and radical resection is required. Despite this, recurrence is frequent. Conclusions: The particularly aggressive form of this pathology, with extensive local invasion and poor response to the initial oncoespecific treatment, stands out in the analyzed case

Humans , Male , Middle Aged , Anus Neoplasms/surgery , Carcinoma, Verrucous/surgery , /methods , Anal Canal/pathology , Anus Neoplasms/drug therapy , Carcinoma, Verrucous/drug therapy , Neoadjuvant Therapy
J. coloproctol. (Rio J., Impr.) ; 39(2): 127-131, Apr.-June 2019. tab, ilus
Article in English | LILACS (Americas) | ID: biblio-1012584


ABSTRACT Objective: To describe the partial results of a study in patients with rectal cancer who underwent neoadjuvant treatment with chemotherapy and radiotherapy regarding the rate of complete clinical response, disease-free survival, anorectal function, and quality of life. Material and methods: This was a prospective study from June 2015 to June 2018, in patients with low- or mid-rectum adenocarcinoma and clinical stage II or III, treated with radiotherapy and chemotherapy (IMRT 54 Gy for six weeks) concomitant with 5-fluorouracil (5-FU) 380 mg/m2 and folinic acid (LV) 20 mg/m2 for five days in the first and fifth weeks and two cycles after radiotherapy (5-FU 400 mg/m2 and LV 20 mg/m2) every 28 days. After the treatment, clinical examination, rectosigmoidoscopy, pelvic magnetic resonance imaging, chest and upper abdomen computed tomography, and CEA testing were performed. Resection surgery was performed in those with incomplete clinical response (iCR). Those with complete clinical response (cCR) are under observation (wait-and-see policy). Manometry and scintigraphic function and quality of life scales were collected before treatment and at 30 and 90 days after the end of treatment. Results: As of June 2018, 11 patients were recruited. One was excluded from the analysis for presenting severe toxicity, suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency, after the first chemotherapy cycle. All others completed the treatment. Two patients presented toxicity grade 3/4 related to chemotherapy and had their doses reduced. Seven patients (70%) presented iRC; three underwent rectosigmoidectomy, and the anatomopathological evaluation indicated complete pathological response in two cases (28.5%). Three (30%) presented cCR and did not present evidence of disease after a mean follow-up of 19 months. Patients presented improvement of anorectal function and quality of life. Conclusions: Advances in the neoadjuvant treatment of rectal tumors contributed to better rates of complete pathological responses. New paradigms promote an increase in the complete clinical response rates, which would allow organ preservation and consequent reduction of surgical morbidity.

RESUMO Objetivo: Descrever os resultados parciais de estudo em pacientes com câncer de reto submetidos a tratamento neoadjuvante com quimioterapia e radioterapia quanto à taxa resposta clínica completa, sobrevida livre de doença, função anorretal e qualidade de vida. Material e métodos: Estudo prospectivo desde junho 2015 até junho de 2018, em paciente com adenocarcinoma de reto baixo ou médio e estadio clínico II ou III tratados com RT/QT (IMRT 54 Gy em 6 semanas) concomitante a 5-Fuorouracil (5-FU) 380 mg/m2 e ácido folínico (LV) 20 mg/m2 por 5 dias nas primeira e quinta semanas e dois ciclos após RT (5-FU 400 mg/m2 e LV 20 mg/m2) a cada 28 dias. Após o tratamento, realizou-se exame clínico, retossigmoidoscopia, RNM de pelve, TC de tórax e abdômen superior e dosagem de CEA. Naqueles com Resposta Clínica Incompleta (iRC) procedeu-se à cirurgia de ressecção. Aqueles com Resposta Completa (cRC) estão em observação (wait and see policy). Manometria e escalas de função esfincteriana e qualidade de vida foram obtidas antes e após 30 e 90 dias do término do tratamento. Resultados: Até junho de 2018, recrutaram-se 11 pacientes. Um foi excluído da análise, pois apresentou toxicidade severa sugestiva de deficiência de DPD após o primeiro ciclo de QT. Todos os demais concluíram o tratamento. Toxicidades graus 3/4 relacionadas à QT ocorreram dois pacientes, reduzindo-se sua dose. Sete (70%) apresentaram iRC, submetendo três à retossigmoidectomia cuja avaliação anatomopatológica evidenciou Resposta Completa (pRC) em dois casos (28,5%). Três (30%) apresentaram cRC e estão sem evidência de doença com seguimento médio de 19 meses. Houve melhora da função anorretal e da qualidade de vida. Conclusões: Avanços no tratamento neoadjuvante dos tumores de reto contribuíram para melhores taxas de pRC. Novos paradigmas promovem crescentes índices de cRC, o que possibilitaria a preservação do órgão e consequente redução da morbidade cirúrgica.

Humans , Male , Female , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Neoadjuvant Therapy , Quality of Life , Rectum/surgery
J. coloproctol. (Rio J., Impr.) ; 39(2): 178-183, Apr.-June 2019.
Article in English | LILACS (Americas) | ID: biblio-1012583


ABSTRACT Study objectives: To evaluate the ideal timing between neoadjuvant therapy and surgical treatment of rectal cancer, as well as the influence on treatment outcomes. Methods: Using PubMed, a systematic literature search was made on the influence of surgery timing after chemoradiotherapy in treating rectal cancer. Results and discussion: A total of 34 articles published until April 2017 were analyzed. Nine of them were randomized clinical trials, one was a non-randomized trial, 23 were retrospective studies, and one was a meta-analysis. These studies compared treatment intervals varying between two and 19 weeks. Intervals of nine to 14 weeks showed increased tumor downstaging and higher rates of complete pathological response. These intervals shown safety for patients. Nonetheless, few studies showed differences in overall survival. The most used intervals between neoadjuvant chemoradiotherapy are six to eight weeks. Despite that, intervals longer than these show potential benefits for patients without putting them at risk of disease progression. Studies evaluating the effect of overall survival and long-term recurrence are scarce. Conclusion: Programming surgery more than eight weeks after chemoradiotherapy seems preferable to the six to eight weeks most recently practiced, increasing tumor downstaging and having higher complete pathological response rates.

RESUMO Objetivos do estudo: Avaliar o timing ideal entre a terapêutica neoadjuvante e cirúrgica no carcinoma do reto e a sua influência nos outcomes de tratamento. Material e métodos: Utilizando a "PubMed", foi feita uma revisão sistemática da literatura disponível acerca da influência do timing cirúrgico após quimiorradioterapia neoadjuvante no tratamento do carcinoma do reto. Resultados e discussão: Foram analisados 34 artigos publicados até Abril de 2017, sendo que destes nove foram ensaios clínicos randomizados, um foi ensaio clínico não randomizado, 23 foram estudos retrospetivos e um foi uma meta-análise. Estes estudos compararam intervalos de tratamento que variaram entre 2 e 19 semanas. Intervalos entre as 9-14 semanas demonstraram aumento do downstaging tumoral e da taxa de resposta patológica completa. Estes intervalos demonstraram segurança para os doentes. Contudo, poucos estudos demonstraram diferenças na sobrevida dos doentes. Os intervalos mais usados entre a QRT neoadjuvante e o tratamento cirúrgico são de 6-8 semanas. Apesar disso, intervalos superiores às 6-8 semanas demonstram potenciais benefícios para os pacientes sem os colocar em risco de progressão da doença. São limitados os estudos que avaliam o efeito na sobrevida e recorrência em longo prazo. Conclusão: A programação da cirurgia superior às 8 semanas após quimiorradioterapia parece ser preferível às 6-8 semanas até recentemente praticada, aumentando o downstaging tumoral e a taxa de resposta patológica completa.

Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/therapy , Radiotherapy , Surgical Procedures, Operative , Neoadjuvant Therapy , Drug Therapy
Rev. argent. mastología ; 38(137): 85-97, abr. 2019. graf
Article in Spanish | LILACS (Americas) | ID: biblio-1116972


Introducción La quimioterapia neoadyuvante (qtn) es el tratamiento inicial para pacientes con tumores localmente avanzados, permitiendo la evaluación de la sensibilidad in vivo a los agentes antineoplásicos y la planificación de estrategias quirúrgicas con resultados cosméticos favorables. Objetivos Comparar la tasa de respuesta patológica completa (pcr), la tasa de conversión a cirugía conservadora (tccc), el tiempo a la recaída a distancia (trad) y la supervivencia libre de enfermedad a distancia (sled) a 60 meses en pacientes con cáncer de mama Estadio III que fueron tratadas con qtn antes y después del año 2007 Material y método Se trata de un estudio observacional de cohortes retrospectivo en el que se analizaron registros de pacientes con cáncer de mama Estadio III operadas entre 1987 y 2016 que hubieran realizado qtn . Se constituyeron dos cohortes: en la primera se reunieron pacientes tratadas entre 1987 y 2006; en la segunda se agruparon aquellas tratadas entre 2007 y 2016. Se estableció esta diferencia dado que a partir de 2007 hubo cambios en la modalidad terapéutica: se administró la quimioterapia en forma continua antes de la cirugía y se introdujeron los taxanos y la terapia anti-her2 neu en los esquemas de qtn . En total se registraron 202 pacientes, 146 pertenecientes a la primera cohorte y 56 pertenecientes a la segunda. La mediana de edad y el tamaño tumoral fueron similares entre ambos grupos, mientras que en el segundo grupo observamos mayor porcentaje de tumores Grado 3 y mayor carga tumoral axilar. Resultados La tasa de pcr fue del 2% (n=3) para el primer grupo y de 13% (n=7) para el segundo (p=0,0022). La tasa de conversión a cirugía conservadora fue del 27% (n=20) para el primer grupo y del 41% (n=17) para el segundo, observándose un 14% más de cirugías conservadoras en este último (p=0,11). La mediana de trad fue de 33 meses para el primer grupo y de 46,5 meses para el segundo (p=0,044). La sled a 60 meses fue del 58% vs el 74% para el primer y segundo grupo respectivamente (p=0,039). Conclusiones Los cambios en la modalidad terapéutica en qtn en nuestra práctica se tradujeron en mayores tasas de pcr, mayor porcentaje de conversión a cirugía conservadora, mayor tiempo a la recidiva a distancia y mayor supervivencia libre de enfermedad a distancia

Introduction Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer, allowing surgical planning with favorable cosmetic outcome and evaluation of in vivo response to antineoplastic agents. Objectives To compare pathologic complete response, breast conserving surgery conversion rates, time to distant relapse and distant recurrence free survival after 60 months in patients with Stage III breast cancer who received neoadjuvant chemotherapy before and after year 2007. Materials and method Observational retrospective cohort study analizing database and medical records of patients with Stage III breast cancer who had surgery after neoadjuvant therapy between 1987 and 2016. We divided the population into two cohorts, one with patients treated between 1987 and 2006, and another one with those ones treated between 2007 and 2016. We established that difference given that from 2007 and onwards there were major changes in treatment modality: chemotherapy was administered completely before surgery, and Taxane-containing regimens as well as Anti-her2 therapies were included. We registered 202 patients, 146 in the first group and 56 in the second. While median of age and tumor size were similar between groups, axillary tumor burden and histologic grade were higher in the second group. Results Pathologic complete response rate was 2% for the first group and 13% for the second (p=0.0022). Breast conserving surgery conversion rates were 27% vs 41%, with 14% more breast conserving surgeries in the second cohort. Median time to distant recurrence was 33 months vs 46.5 months (p=0.044) and distant recurrence free survival was 58% vs 74% (p=0.039) for groups 1 and two 2 respectively. Conclusions Changes in treatment modality in our practice resulted in better pcr outcomes, more breast conserving surgery conversion rates, longer time to distant relapse and a better distant recurrence free survival

General Surgery , Breast Neoplasms , Neoadjuvant Therapy , Neoplasms
J. coloproctol. (Rio J., Impr.) ; 39(2): 163-168, Apr.-June 2019. tab, graf
Article in English | LILACS (Americas) | ID: biblio-1012595


ABSTRACT Objectives: To evaluate the rates of abdominoperineal resection in patients with low rectal adenocarcinoma at the Hospital Barão de Lucena - SES/PE. Methodology: This is a study based on the analysis of medical records of patients with low rectal adenocarcinoma submitted to surgical treatment at the Hospital Barão de Lucena Coloproctology Service between 2013 and 2016. Results: It was observed that 77.5% of patients underwent abdominoperineal resection and 22.5% underwent anal sparing surgery. Most of the patients were male (62.5%), were under 70 years old (72.5%), presented a BMI less than 30 kg/m2 (87.5%), presented American Society of Anesthesiologists (ASA) score I and III (82.5%), Rullier classification from I to III (95%) and TNM different from T1-T3 (95%). In 92.5% of medical records, there was no record of fecal continence before surgery. The most frequent period between the end of the radiotherapy and the surgery was over 11 weeks (57.5%); the most common distance from the tumor to the anal margin was between 3.1 and 4.0 cm (35% of patients). Conclusion: There was a high rate of non-sparing anal sphincter surgeries. The only predictive factor for abdominoperineal resection was the presence of tumors classified as Rullier type III and IV.

RESUMO Objetivos: Avaliar a taxa de ressecção abdominoperineal em portadores de adenocarcinoma de reto inferior no Hospital Barão de Lucena - SES/PE. Metodologia: Trata-se de um estudo baseado na análise de prontuários de pacientes com adenocarcinoma de reto inferior submetidos a tratamento cirúrgico no serviço de Coloproctologia do Hospital Barão de Lucena entre 2013 e 2016. Resultados: Observou-se que 77,5% dos pacientes foram submetidos à ressecção abdominoperineal e 22,5% à cirurgia com preservação esfincteriana. A maioria dos pacientes era do sexo masculino (62,5%), tinha menos que 70 anos (72,5%), apresentava IMC menor que 30 kg/m2 (87,5%), apresentava ASA I e II (82,5%), classificação de Rullier de I a III (95%) e TNM diferente de T1-T3 (95%). Em 92,5% dos prontuários, não havia registro sobre a continência fecal antes da cirurgia. O período mais frequente entre o término da radioterapia e a realização da cirurgia foi superior a 11 semanas (57,5%); a distância, mais comum, do tumor à margem anal estava entre 3,1-4,0 cm (35% dos pacientes). Conclusão: Houve uma alta taxa de cirurgias não poupadoras de esfíncter anal. O único fator preditivo para a realização da ressecção abdominoperineal foi a presença de tumores classificados como Rulier tipo III e IV.

Humans , Male , Female , Rectal Neoplasms/surgery , Colorectal Surgery , Magnetic Resonance Imaging , Neoadjuvant Therapy
Korean Journal of Radiology ; : 1003-1018, 2019.
Article in English | WPRIM (Western Pacific) | ID: wprim-760291


Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.

Chemoradiotherapy , Humans , Magnetic Resonance Imaging , Methods , Neoadjuvant Therapy , Quality of Life , Rectal Neoplasms
Article in English | WPRIM (Western Pacific) | ID: wprim-742340


BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has become the standard of care for esophageal cancer patients prior to esophagectomy. However, the optimal timing for surgery after completion of nCRT remains unclear. METHODS: A retrospective review was performed of patients who underwent esophagectomy with cervical anastomosis for esophageal cancer at a single institution between January 2000 and June 2015. Patients were categorized into 3 cohorts: those who did not receive nCRT prior to esophagectomy (no nCRT), those who underwent esophagectomy within 35 days after nCRT (≤35d), and those who underwent esophagectomy more than 35 days after nCRT (>35d). RESULTS: A total of 366 esophagectomies were performed during the study period, and 348 patients met the inclusion criteria. Anastomotic leaks occurred in 11.8% of all patients included in the study (41 of 348). Within each cohort, anastomotic leaks were detected in 14.7% of patients (17 of 116) in the no nCRT cohort, 7.3% (13 of 177) in the ≤35d cohort, and 20.0% (11 of 55) in the >35d cohort (p=0.020). Significant differences in the occurrence of anastomotic leaks were observed between the no nCRT and ≤35d cohorts (p=0.044), and between the ≤35d and >35d cohorts (p=0.007). CONCLUSION: Esophagectomy with cervical anastomosis within 35 days of nCRT resulted in a lower percentage of anastomotic leaks.

Anastomotic Leak , Chemoradiotherapy , Cohort Studies , Esophageal Neoplasms , Esophagectomy , Humans , Incidence , Neoadjuvant Therapy , Retrospective Studies , Standard of Care
Article in English | WPRIM (Western Pacific) | ID: wprim-739582


PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.

Area Under Curve , Breast Neoplasms , Breast , Calibration , Discrimination, Psychological , Drug Therapy , Humans , Logistic Models , Lymph Nodes , Neoadjuvant Therapy , Neoplasm Metastasis , Nomograms , Polymerase Chain Reaction , ErbB Receptors , Receptors, Progesterone