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Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. BACKGROUND: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. PURPOSE: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. METHODS: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. RESULTS: 270 patients were included, 57.8% male and mean age 61.7 (30â88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5â86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). CONCLUSION: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.
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Terapia Neoadjuvante , Recidiva Local de Neoplasia , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Terapia Neoadjuvante/métodos , Prognóstico , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Fatores de Risco , Resultado do Tratamento , Quimiorradioterapia , Estimativa de Kaplan-Meier , Fatores de TempoRESUMO
Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death. Rectal cancer accounts for approximately one-third of new colorectal cancer cases, with adenocarcinoma as the predominant subtype. Despite an overall decline in colorectal cancer incidence and mortality, due to advancements in screening, early diagnosis, and treatment options, there is a concerning increase in incidence rates among young patients. Recent significant advances in managing locally advanced rectal cancer, such as the establishment of different surgical approaches, neoadjuvant treatment using different protocols for high-risk cases, and the adoption of organ-preservation strategies, have increased the importance of the role played by radiologists in locoregional assessment on magnetic resonance imaging at baseline, at restaging, and during active surveillance of patients with rectal cancer. In this article, we review the role of restaging rectal magnetic resonance imaging after neoadjuvant therapy, providing radiologists with a practical, step-by-step guide for assessing treatment response.
O câncer colorretal é o terceiro câncer mais comum e a segunda principal causa de morte relacionada ao câncer. O câncer retal representa aproximadamente um terço dos novos casos de câncer colorretal, sendo o adenocarcinoma o subtipo predominante. Apesar de uma diminuição geral na incidência e mortalidade, impulsionada por avanços na prevenção do câncer, diagnóstico precoce e opções de tratamento aprimoradas, há uma preocupante elevação nas taxas entre os pacientes jovens. Avanços recentes significativos no manejo do câncer retal localmente avançado, como abordagens cirúrgicas, o uso de diferentes protocolos de tratamento neoadjuvante para casos de alto risco e a adoção de estratégias de preservação de órgãos, aumentaram o papel dos radiologistas na avaliação locorregional por meio da ressonância magnética na avaliação inicial, reestadiamento e vigilância ativa de pacientes com câncer retal. Este manuscrito tem como objetivo revisar o papel da ressonância magnética retal no reestadiamento após terapia neoadjuvante, fornecendo aos radiologistas um guia prático para revisar exames nesse contexto.
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The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8+ T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies.
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BACKGROUND: Neoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy-TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. METHODS: This was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)-TNT-arm-or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). RESULTS: Between April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). CONCLUSIONS: TNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Irinotecano , Leucovorina , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Pessoa de Meia-Idade , Masculino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Feminino , Idoso , Brasil , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Adulto , Quimiorradioterapia/métodos , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Conduta Expectante/estatística & dados numéricos , Resultado do Tratamento , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , SeguimentosRESUMO
BACKGROUND: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil. Its standard treatment consists of neoadjuvant chemotherapy (NAC). METHODS: This was a longitudinal study with follow-up performed between the years 2015 and 2017. Thirty women with locally advanced TNBC submitted to NAC, and 30 healthy were included. Peripheral blood samples were collected before NAC (Pre-NAC) and after NAC (Post-NAC). RESULTS: Patients with TNBC had elevated levels of CD28+ T, FAS+ T, CTLA4+ T, PD1+ T, CD28+CD4+ T, PD1+CD4+ T and CD8+ T and PD1+ CD8+ T cells compared to controls (p < 0.05). Patients with pathological complete response (pCR) had low FAS+ T cells, FAS+CD4+ T cells, and PD1+CD8+ T cells compared to the non-pCR (p < 0.05). Significant differences were observed in the levels of CD28+ T cells, FAS+ T and PD1+ T, CD4+ T, CD28+CD4+ T, FAS+CD4+ T, PD1+CD4+ T, CD8+ T, and PD1+CD8+ T cells between Pre-NAC and Post-NAC groups (p < 0.05). CONCLUSION: Alterations in the circulating FAS+CD4+ T and PD1+CD8+ T cell levels Pre-NAC are associated with pCR, suggesting potential predictive biomarkers of NAC response in TNBC. The largest changes in the cellular immune response profile Post-NAC showed that chemotherapy treatment can modulate the immune response and that it is associated with prognosis in TNBC.
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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
PURPOSE: Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients' overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS. MATERIALS AND METHODS: IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS. RESULTS: Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B-like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor-positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS. CONCLUSION: NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Antígeno Ki-67 , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Gradação de Tumores , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , PrognósticoRESUMO
BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.
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Introduction: After the diagnosis of neoplasm of the middle and distal rectum, patients are often submitted to oncological treatment by neoadjuvant therapy. At the end of this treatment, those patients who show complete clinical response can choose, together with their physician, to adopt the watch-and-wait strategy; although it implies lower morbidity for the patient, this strategy is dependent on strict adherence to treatment follow-up for the early identification of any future local injury. Materials and Methods: Survey of data from medical records and description, and discussion of case reports with a literature review in books and databases. Results: We report the case of a 73-year-old patient diagnosed with moderately differentiated adenocarcinoma of the middle rectum, Stage II (cT3bN0M0), who presented complete clinical response after undergoing treatment with neoadjuvant therapy. Together with the assistant team, the watch-and-wait strategy was chosen. During the follow-up, an endoscopic examination showed a vegetating at the proximal limit of the tumor scar. We chose to perform submucosal endoscopic dissection. The report of the anatomopathological examination evidenced a serrated adenoma with narrow margins free of neoplasia. Conclusion: Patient adherence to cancer treatment using the watch-and-wait strategy is essential for the early identification of new local lesions. After resection of the lesion identified in the tumor scar site as a neoplasm-free lesion, it is consistent to think that this lesion would be the origin of the neoplasm, given the adenomatous origin. (AU)
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Feminino , Idoso , Reto/lesões , Diagnóstico Diferencial , Neoplasias Retais/terapia , Terapia Neoadjuvante , EndoscopiaRESUMO
Abstract Objective Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Conclusion Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario.
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Introducción: La quimioterapia previa o en curso puede presentar una amplia gama de interacciones, que aumentan el efecto clínico y la toxicidad de fármacos utilizados en quimioterapia, como los anestésicos. Objetivo: Evaluar la influencia de la anestesia sobre las pacientes con neoplasia de mama que recibieron o no quimioterapia neoadyuvante. Métodos: Se realizó un estudio cuasiexperimental, prospectivo, de corte longitudinal en el Servicio de Anestesiología y Reanimación del Hospital Clínico Quirúrgico Hermanos Ameijeiras, durante el período comprendido de enero de 2021 a enero de 2023. Resultados: La edad promedio fue 53,2 años en el Grupo I y 55,4 años en el II. En ambos grupos predominaron los pacientes ASA II, con 92,0 % en el I y 88,0 % en el II. El 92,0 % de las pacientes del Grupo I y el 96,0 % de los del Grupo II recibieron anestesia balanceada. La arritmia (20 %), seguida de prolongación del segmento QT, (4,0 %), la hipertensión arterial (4,0 %), la oliguria (16,0 %) y el dolor posoperatorio (12,0 %) fueron las complicaciones más frecuentes en los pacientes que recibieron quimioterapia neoadyuvante. En cuanto a la gravedad, en el 56 % de los pacientes fue severa. El 44 % de las complicaciones (arritmias, prolongación QT e hipertensión arterial y oliguria) aparecieron de manera mediata en el posoperatorio. Conclusiones: Se evaluó la influencia de la anestesia sobre las pacientes con neoplasia de mama que recibieron o no quimioterapia neoadyuvante, y se identificaron las complicaciones asociadas a la conducta anestésica.
Introduction: Drugs used for chemotherapy treatment in the cancer patient may increase the clinical effect and toxicity of anesthetics. Objective: To evaluate the clinical response of anesthesia in female patients operated on for breast cancer who received neoadjuvant chemotherapy. Methods: A quasiexperimental, prospective, longitudinal and controlled study was carried out at the anesthesiology and resuscitation service of Hospital Clínico Quirúrgico Hermanos Ameijeiras, during the period from January 2021 to January 2023. Results: Fifty patients were evaluated, whose average ages were 53.2 years in Group I and 55.4 years in Group II. Both groups were dominated by patients with American Society of Anesthesia Grade II criteria (92.0 % vs. 88.0 %). Balanced anesthesia was received by 92.0 % of the patients in Group I and 96.0 % of those in Group II. In terms of safety, arrhythmia (20.0 %), QT segment prolongation (4.0 %), arterial hypertension (4.0 %), oliguria (16.0 %) and postoperative pain (12.0 %) were predominant in relation to previous treatment. 56.0 % were grade IV or severe and 44.0 % (arrhythmias, QT prolongation and arterial hypertension and oliguria) had postoperative mediated onset. Conclusions: Complications due to anesthetic agents in patients with neoadjuvant chemotherapy for breast cancer are more frequent and severe. Complications were identified in relation to the administration of anesthesia.
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ABSTRACT Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS.
RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.
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ABSTRACT BACKGROUND: Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor. AIMS: To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting. METHODS: The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded. RESULTS: Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%). CONCLUSIONS: The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.
RESUMO RACIONAL: Apesar da preferência pelo tratamento multimodal para o câncer gástrico, o abandono do tratamento quimioterápico bem como a necessidade de cirurgia "upfront" em pacientes obstruídos traz impactos negativos para o tratamento. A dificuldade de acesso ao tratamento em centros especializados no Sistema Único de Saúde (SUS) é um agravante. OBJETIVOS: Identificar vantagens, fatores prognósticos, complicações e sobrevida de terapias neoadjuvantes e adjuvantes no tratamento do câncer gástrico no cenário do SUS. MÉTODOS: Estudo retrospectivo incluindo 81 pacientes com adenocarcinoma gástrico submetidos a tratamento segundo os protocolos INT0116 (quimiorradioterapia adjuvante), CLASSIC (quimioterapia adjuvante), FLOT4-AIO (quimioterapia perioperatória) e cirurgia com intuito curativo (ressecção R0 e linfadenectomia D2) em um único centro oncológico entre 2015 e 2020. Indivíduos com outros tipos histológicos, coto gástrico, câncer de esôfago, outros protocolos de tratamento e estádio Ia ou IV foram excluídos. RESULTADOS: Os pacientes foram distribuídos em: FLOT4-AIO (26 pacientes), CLASSIC (25 pacientes) e INT0116 (30 pacientes). A média de idade foi 61 anos. Mais de 60% dos pacientes apresentaram estádio III patológico. A taxa de completude do tratamento foi 56%. A taxa de resposta patológica completa do grupo FLOT4-AIO foi 7,7%. Dentre os fatores prognósticos que impactaram a sobrevida global e sobrevida livre de doença tivemos etilismo, complicações pós-operatórias precoces, status anatomopatológico pN2 e pN3. A taxa de sobrevida global em 3 anos foi 64,9% sendo o subgrupo CLASSIC com melhor sobrevida (79,8%). CONCLUSÕES: A estratégia de tratamento do câncer gástrico varia de acordo com a necessidade de cirurgia inicial. O subgrupo CLASSIC apresentou melhor sobrevida global e sobrevida livre de doença. O esquema INT0116 também protegeu contra a mortalidade, mas não com significância estatística. Apesar do FLOT4-AIO ser o tratamento de escolha, a dificuldade na realização da neoadjuvância no âmbito do SUS impactou negativamente nos resultados devido à criticidade da ingesta alimentar e à pior tolerância ao tratamento.
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Abstract Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death. Rectal cancer accounts for approximately one-third of new colorectal cancer cases, with adenocarcinoma as the predominant subtype. Despite an overall decline in colorectal cancer incidence and mortality, due to advancements in screening, early diagnosis, and treatment options, there is a concerning increase in incidence rates among young patients. Recent significant advances in managing locally advanced rectal cancer, such as the establishment of different surgical approaches, neoadjuvant treatment using different protocols for high-risk cases, and the adoption of organ-preservation strategies, have increased the importance of the role played by radiologists in locoregional assessment on magnetic resonance imaging at baseline, at restaging, and during active surveillance of patients with rectal cancer. In this article, we review the role of restaging rectal magnetic resonance imaging after neoadjuvant therapy, providing radiologists with a practical, step-by-step guide for assessing treatment response.
Resumo O câncer colorretal é o terceiro câncer mais comum e a segunda principal causa de morte relacionada ao câncer. O câncer retal representa aproximadamente um terço dos novos casos de câncer colorretal, sendo o adenocarcinoma o subtipo predominante. Apesar de uma diminuição geral na incidência e mortalidade, impulsionada por avanços na prevenção do câncer, diagnóstico precoce e opções de tratamento aprimoradas, há uma preocupante elevação nas taxas entre os pacientes jovens. Avanços recentes significativos no manejo do câncer retal localmente avançado, como abordagens cirúrgicas, o uso de diferentes protocolos de tratamento neoadjuvante para casos de alto risco e a adoção de estratégias de preservação de órgãos, aumentaram o papel dos radiologistas na avaliação locorregional por meio da ressonância magnética na avaliação inicial, reestadiamento e vigilância ativa de pacientes com câncer retal. Este manuscrito tem como objetivo revisar o papel da ressonância magnética retal no reestadiamento após terapia neoadjuvante, fornecendo aos radiologistas um guia prático para revisar exames nesse contexto.
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Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.
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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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Pathological complete response (pCR) is an important surrogate outcome to assess the effects of neoadjuvant chemotherapy (NAC). Nomograms to predict pCR have been developed with local data to better select patients who are likely to benefit from NAC; however, they were never critically reviewed regarding their internal and external validity. The purpose of this systematic review was to critically appraise nomograms published in the last 20 years (2010-2022). Articles about nomograms were searched in databases, such as PubMed/MEDLINE, Embase and Cochrane. A total of 1120 hits were found, and seven studies were included for analyses. No meta-analysis could be performed due to heterogeneous reports on outcomes, including the definition of pCR and subtypes. Most nomograms were developed in Asian centers, and nonrandomized retrospective cohorts were the most common sources of data. The most common subtype included in the studies was triple negative (50%). There were articles that included HER2+ (>80%). In one study, scholars performed additional validation of the nomogram using DFS and OS as outcomes; however, there was a lack of clarity on how such endpoints were measured. Nomograms to predict pCR cannot be extrapolated to other settings due to local preferences/availability of NAC. The main gaps identified in this review are also opportunities for future nomogram research and development.
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Neoplasias da Mama , Nomogramas , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos RetrospectivosRESUMO
Introduction: Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. Objective: To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. Materials and methods: We performed a retrospective analysis of non-metastatic HER2-positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Results: Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR =0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti-HER2 therapy than in those with chemotherapy alone (48% versus 16%). Conclusions: In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptores de Progesterona/uso terapêutico , Receptor ErbB-2/uso terapêutico , Receptores de Estrogênio/uso terapêutico , Estudos Retrospectivos , Colômbia , Resultado do Tratamento , Anticorpos Monoclonais Humanizados , Trastuzumab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
OBJECTIVES: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. METHODS: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the KaplanâMeier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. RESULTS: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). CONCLUSION: The pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.