Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

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.

Strategy and Status of Neoadjuvant Therapy for HER2-positive Breast Cancer / 肿瘤防治研究

Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

Complete pathological response in patients with HER2 positive breast cancer treated with neoadjuvant therapy in Colombia / Respuesta patológica completa de pacientes con cáncer de mama HER2 positivo tratadas con quimioterapia neoadyuvante en Colombia

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%). Conclusion. 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.

Introducción. El adenocarcinoma de seno es el tipo de cáncer más frecuente y con mayor tasa de mortalidad asociada en mujeres en Colombia. Aproximadamente entre el 15 al 20 % de estos cánceres sobreexpresan el gen HER2. Objetivo. Analizar las asociaciones existentes entre múltiples variables clínicas e histológicas con respecto a la respuesta patológica completa en pacientes con cáncer de mama HER2 positivo que fueron tratadas con quimioterapia neoadyuvante en un centro especializado en el tratamiento del cáncer en Colombia. Materiales y métodos. Se realizó un análisis retrospectivo de las pacientes con cáncer de mama HER2 positivo, no metastásicas, que recibieron quimioterapia neoadyuvante entre el 2007 y el 2020 en el Instituto de Cancerología Las Américas Auna (Medellín, Colombia). Se evaluaron los parámetros de grado tumoral, índice de proliferación, estatus de receptores de estrógeno y de progesterona, tipo de quimioterapia neoadyuvante recibida, tasas de respuesta patológica completa y supervivencia global. Resultados. Las variables asociadas con tasas de respuesta patológica completa más bajas fueron grados tumorales 1-2 (OR = 0,55; IC 95% = 0,37-0,81; p= 0,03), positividad de receptores de estrógeno (OR = 0,65; IC 95 % = 0,43-0,97; p = 0,04) y positividad de receptores de progesterona (OR = 0,44; IC 95 % = 0,29-0,65; p = 0,0001). La positividad fuerte para HER2 (puntaje 3+) se asoció a tasas de respuesta patológica completa más altas (OR = 3.3; IC 95 % = 1,3-8,35; p = 0,013). La supervivencia global a cinco años fue del 91,5 % (IC 95 % = 82,6-95,9) en pacientes con respuesta patológica completa y del 73,6 % (IC 95 % = 66.4-79.6) en pacientes sin respuesta patológica completa (p = 0.001). La tasa de respuesta patológica completa fue tres veces mayor en los pacientes que recibieron quimioterapia neoadyuvante con terapia anti-HER2 comparado con aquellos que recibieron quimioterapia sola sin agentes anti-HER2 (48 % versus 16 %). Conclusión. En pacientes con cáncer de mama con sobreexpresión de HER2, grado tumoral tres, receptores de estrógeno y progesterona negativos, positividad fuerte para HER2 (puntaje 3+) y uso de quimioterapia neoadyuvante con trastuzumab se asociaron con mayores tasas de respuesta patológica completa.

Oncological outcomes of visibly complete transurethral resection prior to neoadjuvant chemotherapy for bladder cancer

ABSTRACT Purpose: To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods: We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (<ypT2N0), with complete pathologic response (ypT0N0) and survival as secondary endpoints. Logistic regression and Cox proportional hazards models were utilized. Results: We identified 153 patients, including 116 (76%) with a complete TURBT. Sixty-four (42%) achieved <ypT2N0 and 43 (28%) achieved ypT0N0. When comparing those with and without a complete TURBT, there was no significant difference in the proportion with <ypT2N0 (43% vs 38%, P=0.57) or ypT0N0 (28% vs 27%, P=0.87). After median follow-up of 3.6 years (IQR 1.5-5.1), 86 patients died, 37 died from bladder cancer, and 61 had recurrence. We did not observe a statistically significant association of complete TURBT with cancer-specific or recurrence-free survival (p≥0.20), although the hazard of death from any cause was significantly higher among those with incomplete TURBT even after adjusting for ECOG and pathologic T stage, HR 1.77 (95% CI 1.04-3.00, P=.034). Conclusions: A visibly complete TURBT was not associated with pathologic downstaging, cancer-specific or recurrence-free survival following NAC and RC. These data do not support the need for repeat TURBT to achieve a visibly complete resection if NAC and RC are planned.

Evaluation of the response rate to neoadjuvant chemoradiotherapy in patients with rectal adenocarcinoma: a retrospective long-term study in two terciary reference centers

Objectives: To evaluate the complete response (CR) rate and surgeries performed in patients with rectal adenocarcinoma who underwent neoadjuvant therapy (NT) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Hospital São Paulo, in Ribeirão Preto, from January 2007 to December 2017. Methods: We evaluated 166 medical records of patients with locally advanced rectal adenocarcinoma (T3, T4 or N+) who underwent NT. The regimen consisted of performing conventional (2D) or conformational (three-dimensional-3D/ radiotherapy with modulated intensity - IMRT) at a dose of 45-50.4Gy associated with capecitabine 1650mg/m2 or 5-fluorouracil (5FU) and leucovorin (LV). The following variables were analyzed: gender, age, pretreatment stage, radiotherapy, CR index, local and distant recurrence rates. Surgical treatment and complications were also evaluated. Results: The CR index was 28.3%. Patients treated with 3D/IMRT radiotherapy had a higher rate of CR (36.3% x 4.8%; p < 0.001), higher rates of clinical follow-up (21% x 0%; p < 0.001), lower surgery rates (79% x 100%; p < 0.001), higher rates of transanal resection (37.1% x 9.5%; p = 0.001), lower rates of abdominal rectosigmoidectomy (25.8% x 50%; p = 0.007) and lower rates of abdominoperineal resection of the rectum (16.1% x 40.5%; p = 0.002), when compared to patients treated with 2D radiotherapy. Conclusion Modern radiotherapy techniques such as 3D conformal and IMRT, by offering greater adequacy and precision of treatment, could result in better local control and less toxicity in organs at risk, enabling organ preservation strategies and less invasive approaches in selected cases. (AU)

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Respuesta tumoral a la quimioterapia neoadyuvante en subtipos moleculares de cáncer de mama en Medellín, Colombia. Estudio de cohorte retrospectivo / Tumor response to neoadjuvant chemotherapy in molecular breast cancer subtypes in Medellin, Colombia. Retrospective cohort study

Objetivos: Describir la frecuencia de la respuesta clínica y patológica, entre los diferentes subtipos moleculares de cáncer de mama, en pacientes que previamente recibieron quimioterapia neoadyuvante. Materiales y métodos: Cohorte retrospectiva, descriptiva. Se incluyeron mujeres mayores de 18 años, con diagnóstico histológico de carcinoma invasivo de mama, en estadios IIA, IIB, IIIA, IIIB y IIIC, con clasificación por subtipos moleculares, que hubieran recibido quimioterapia neoadyuvante, atendidas en una clínica de alto nivel de complejidad localizada en Medellín (Colombia), entre el 1 de julio de 2017 y el 30 de julio de 2019. Las variables recolectadas fueron edad, estadio clínico, características histológicas, clasificación molecular y la respuesta clínica y patológica completa por subtipo molecular. Se realizó análisis descriptivo. Resultados: 255 pacientes cumplieron con los criterios de inclusión. La edad media fue de 55,2 años; los estadios clínicos con mayor prevalencia fueron IIIB (28,6 %) y IIB (26,3 %), respecto al grado histológico, los más frecuentes fueron grado 3 (48,2 %) y 2 (37,3 %). La frecuencia por subtipos moleculares fue: luminal A (10,2 %), luminal B HER2 negativo (39,6 %), triple negativo (23,1 %), luminal B HER2 positivo (13,7 %), y HER2 puro (13,3 %). La respuesta clínica completa posquimioterapia por subtipo molecular fue: luminal A (26,9 %), luminal B HER2 negativo (37,6 %), luminal B HER2 positivo (48,6 %), HER2 puro (41,2 %), triple negativo (45,8 %); se logró respuesta patológica completa por subtipo molecular, así: luminal A (19,2 %), luminal B HER2 negativo (32,7 %), luminal B HER2 positivo (54,3 %), HER2 puro (50 %), triple negativo (42,4 %). Conclusiones: En la práctica clínica, la clasificación por subtipos moleculares en cáncer de mama permite hacer una aproximación a la respuesta de la quimioterapia neoadyuvante. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Objectives: To describe the frequency of clinical and pathological response in different molecular subtypes of breast cancer, in patients receiving prior neoadjuvant chemotherapy. Materials and methods: Descriptive retrospective cohort. The study population consisted of women 18 years of age and older with a histological diagnosis of invasive breast cancer stages IIA, IIB, IIIA, IIIB and IIIC, with a classification by molecular subtypes, who had received prior neoadjuvant chemotherapy, seen at a high complexity clinic in Medellin (Colombia), between July 1, 2017, and July 30, 2019. We measured age clinical stage, histological characteristics, molecular classification, and complete clinical and pathological responses by molecular subtype. A descriptive analysis was conducted. Results: Overall, 255 patients met the inclusion criteria. Mean age was 55.2 years; the clinical stages with the highest prevalence were IIIB (28.6 %) and IIB (26.3 %), and the most frequent by histologic grading were grades 3 (48.2 %) and 2 (37.3 %). Frequency by molecular types was as follows: luminal A (10.2 %), HER2-negative luminal B (39.6 %), triple-negative (23.1%), HER2-positive luminal B (13.7 %), and pure HER2 (13.3 %). Complete clinical response following chemotherapy, by molecular type, was as follows: luminal A (26.9 %), HER2-negative luminal B (37.6 %), HER2-positive luminal B (48.6 %), pure HER2 (41.2 %), triple-negative (45.8 %). Complete pathological response by molecular subtype was achieved in the luminal A (19.2 %), HER2-negative luminal B (32.7 %), HER2-positive luminal B (54.3 %), pure HER2 (50 %) and triple-negative (42.4 %) subtypes. Conclusions: In clinical practice, breast cancer classification by molecular subtypes is a means to approach the assess the to neoadjuvant chemotherapy. Se requieren estudios prospectivos en la región para determinar la capacidad predictiva de la respuesta patológica completa respecto a la sobrevida global y libre de enfermedad.

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer

SUMMARY OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.

A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy

SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

The effect of positron emission tomography/computed tomography in axillary surgery approach after neoadjuvant treatment in breast cancer

SUMMARY OBJECTIVE: The aim of this study was to determine the role of positron emission tomography/computed tomography in the decision to perform axillary surgery by comparing positron emission tomography/computed tomography findings with pathology consistency after neoadjuvant chemotherapy. METHODS: Patients who were diagnosed for T1-4, cN1/2 breast cancer receiving neoadjuvant chemotherapy in our clinic between January 2016 and February 2021 were evaluated. Clinical and radiological responses, axillary surgery, and histopathological results after neoadjuvant chemotherapy were evaluated. RESULTS: Axillary involvement was not detected in positron emission tomography/computed tomography after neoadjuvant chemotherapy in 140 (60.6%) of 231 node-positive patients. In total, 88 (62.8%) of these patients underwent sentinel lymph node biopsy, and axillary lymph node dissection was performed in 29 (33%) of these patients upon detection of 1 or 2 positive lymph nodes. The other 52 (37.1%) patients underwent direct axillary lymph node dissection, and no metastatic lymph nodes were detected in 33 (63.4%) patients. No metastatic lymph node was found pathologically in a total of 92 patients without involvement in positron emission tomography/computed tomography, and the negative predictive value was calculated as 65.7%. Axillary lymph node dissection was performed in 91 (39.4%) patients with axillary involvement in positron emission tomography/computed tomography after neoadjuvant chemotherapy. Metastatic lymph nodes were found pathologically in 83 of these patients, and the positive predictive value was calculated as 91.2%. CONCLUSION: Positron emission tomography/computed tomography was found to be useful in the evaluation of clinical response, but it was not sufficient enough to predict a complete pathological response. When planning axillary surgery, axillary lymph node dissection should not be decided only with a positive positron emission tomography/computed tomography. Other radiological images should also be evaluated, and a positive sentinel lymph node biopsy should be the determinant of axillary lymph node dissection.

Oncological safety of nipple-sparing mastectomy after neoadjuvant chemotherapy: a systematic review / Segurança oncológica da mastectomia conservadora do mamilo após quimioterapia neoadjuvante: revisão sistemática

ABSTRACT Background: the use of nipple-sparing mastectomy (NSM) in local advanced breast cancer after neoadjuvant chemotherapy (NQT) is increasing, despite few studies on the subject. The aim of this systematic review was to determine the safety of NSM after neoadjuvant chemotherapy. Methods: for this systematic review we searched MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase and Scopus. A literature search of all original studies including randomized controlled trials, cohort studies and case-control studies comparing women undergoing NSM after neoadjuvant chemotherapy for breast cancer was undertaken. Outcomes were locoregional recurrence (LRR), nipple recurrence and distant recurrence (DR). Data analysis was undertaken to explore the safety of NSM after NQT. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021276778. Findings: a total of 437 articles were identified. Four articles were included with 1466 patients all of which had a high to serious risk of overall bias. Local recurrence in the NSM after the NQT group ranged from zero to 9.8%. Nippleareolar complex (NAC) recurrence ranged from zero to 2.1%. The distant recurrence rate ranged from 6.5% to 16%. Due to the lack of pattern among the control groups, it was not possible to perform a meta-analysis. Interpretation: this review provides information for decision making in performing NSM after NQT. Despite the low rates of local recurrence and patients should be counseled about limited oncological information.

RESUMO Introdução: O uso de mastectomia preservadora de complexo aréolo-papilar (MPCAP) no câncer de mama localmente avançado após quimioterapia neoadjuvante (QTN) é crescente, apesar de ainda haver poucos estudos abordando o assunto. O objetivo desta revisão sistemática foi determinar a segurança da MPCAP após a quimioterapia neoadjuvante. Métodos: para esta revisão sistemática, pesquisamos no MEDLINE; Cochrane; Scientific Electronic Library Online (SciELO); Embase e Scopus. Foi realizada uma busca na literatura de todos os estudos originais, incluindo ensaios clínicos randomizados, estudos de coorte e estudos de caso-controle comparando mulheres submetidas a MPCAP após quimioterapia neoadjuvante para câncer de mama. Os desfechos foram recorrência locorregional, recidiva em papila e recorrência à distância. A análise dos dados foi realizada para avaliar a segurança da mastectomia preservadora de complexo aréolo-papilar após o QTN. A qualidade da evidência foi avaliada com a ferramenta de avaliação de risco de viés da Cochrane - ROBINS-I. Este estudo está registrado no PROSPERO, número CRD42021276778. Resultados: Um total de 437 artigos foram identificados. Quatro artigos foram incluídos na análise, totalizando 1466 pacientes, todos com risco de viés geral moderado a alto. A recorrência local no grupo MPCAP após QTN variou de zero a 9,8%. A recorrência no complexo aréolo-papilar (CAP) variou de zero a 2,1%. A taxa de recorrência à distância variou de 6,5% a 16%. Devido à falta de padrão entre os grupos de controle, não foi possível realizar uma meta-análise. Interpretação: esta revisão fornece informações para a tomada de decisão na realização de NSM após QTN. Apesar das baixas taxas de recorrência local, os pacientes devem ser orientados sobre as informações oncológicas limitadas.

Surgical treatment of rectal cancer: prospective cohort study about good oncologic results and low rates of abdominoperineal excision / Tratamento cirúrgico do câncer retal: estudo coorte prospectivo com bons resultados oncológicos e baixas taxas de amputação abdominoperineal

ABSTRACT Objectives: the purpose of this study was to evaluate the outcome of rectal cancer surgery, in a unit adopting the principles of total mesorectal excision (TME) with a high restorative procedure rate and with a low rate of abdominoperineal excision (APE). Methods: we enrolles patients with extraperitoneal rectal cancer undergoing TME or TME+APE. Patients with mid rectal tumors underwent TME, and patients with tumors of the lower rectum and no criteria for APE underwent TME and intersphincteric resection. Those in which the intersphincteric space was invaded and in those with a free distal margin less than 1cm or a tumor free radial margin were unattainable underwent APE or extralevator abdominoperineal excision (ELAPE). We assessed local recurrence rates, overall survival and involvement of the radial margin. Results: sixty (89.6%) patients underwent TME and seven (10.4%) TME + APE, of which five underwent ELAPE. The local recurrence, in pacientes undergoing TME+LAR, was 3.3% and in patients undergoing APE, 14.3%. The local recurrence rate (p=0.286) or the distant recurrence rate (p=1.000) was similar between groups. There was no involvement of radial margins. Survival after 120 months was similar (p=0.239). Conclusion: rectal malignancies, including those located in the low rectum, may be surgically treated with a low rate of APE without compromising oncological principles and with a low local recurrence rates.

RESUMO Objetivos: o objetivo deste estudo foi avaliar os resultados da cirurgia do câncer de reto, em uma unidade que adota os princípios da excisão total do mesorreto (ETM) com baixa taxa de amputação abdominoperineal (AAP). Métodos: os pacientes com câncer retal extraperitoneal foram submetidos a ETM ou ETM com amputação abdominoperianeal. Pacientes com tumores de reto médio foram submetidos a EMT e pacientes com tumores de reto inferior e sem critérios para AAP foram submetidos a EMT e ressecção interesfincteriana. Aqueles em que o espaço interesfincteriano foi invadido e naqueles com margem distal livre menor que 1cm ou margem radial livre de tumor foram inatingíveis foram submetidos a AAP ou excisão abdominoperineal extraelevadora (ELAPE). Avaliamos as taxas de recorrência local, sobrevida global e envolvimento da margem radial. Resultados: sessenta (89,6%) pacientes realizaram ETM e sete (10,4%) ETM + AAP, dos quais cinco realizaram ELAPE. A recidiva local, em pacientes submetidos a ETM com ressecção anterior baixa, foi de 3,3% e em pacientes submetidos a AAP, 14,3%. A taxa de recorrência local (p=0,286) ou a taxa de recorrência à distância (p=1,000) foi semelhante entre os grupos. Não houve envolvimento das margens radiais. A sobrevida após 120 meses foi semelhante (p=0,239). Conclusão: as neoplasias malignas retais, incluindo aquelas localizadas no reto baixo, podem ser tratadas cirurgicamente com baixo índice de AAP, sem comprometer os princípios oncológicos e com baixo índice de recorrência local.

Preoperative chemotherapy versus upfront surgery for advanced gastric cancer: a propensity score matching analysis / Quimioterapia pré-operatória versus cirurgia de princípio para câncer gástrico avançado: análise por escore de propensão

ABSTRACT BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p<0.001), and pTNM stage (p<0.001). Postoperative complications, 30- and 90-days mortality were similar between both groups. Before the propensity score matching analysis, there was no difference in survival between the groups. After the analysis, patients in the preoperative chemotherapy group had better overall survival compared to upfront surgery group (p=0.012). Multivariate analyses demonstrated that American Society of Anesthesiologists III/IV category and the presence of lymph node metastasis were factors significantly associated with worse overall survival. CONCLUSIONS: Preoperative chemotherapy was associated with increased survival in gastric cancer. There was no difference in the postoperative complication rate and mortality compared to upfront surgery.

RESUMO RACIONAL: A ressecção cirúrgica continua sendo a principal modalidade terapêutica curativa para o câncer gástrico avançado. Recentemente, a associação de quimioterapia pré-operatória tem permitido a melhora dos resultados sem aumentar as complicações cirúrgicas. OBJETIVOS: Avaliar os resultados cirúrgicos e oncológicos da quimioterapia pré-operatória em um cenário do mundo real. MÉTODOS: Realizou-se uma revisão retrospectiva de pacientes com câncer gástrico submetidos à gastrectomia. Os pacientes foram divididos em dois grupos para análise: cirurgia inicial e quimioterapia pré-operatória. A análise por escore de propensão, incluindo 9 variáveis, foi aplicada para ajustar possíveis fatores de confusão. RESULTADOS: Dos 536 pacientes incluídos, 112 (20,9%) foram encaminhados para quimioterapia pré-operatória. Antes da análise por escore de propensão, os grupos eram diferentes em termos de idade, nível de hemoglobina, status de node metastasis at clinical stage e extensão da gastrectomia. Após a análise, 112 pacientes foram estratificados para cada grupo. Ambos foram semelhantes para todas as variáveis atribuídas no escore. O grupo da quimioterapia pré-operatória apresentou estágios postoperative p staging (p=0,010), postoperative n staging (p<0,001) e pTNM menos avançados (p<0,001). As complicações pós-operatórias e a mortalidade em 30 e 90 dias foram semelhantes entre os grupos. Antes da análise por escore de propensão, não houve diferença na sobrevida entre os dois grupos. Após a análise, o grupo da quimioterapia pré-operatória apresentou melhor sobrevida global em comparação ao grupo da cirurgia inicial (p=0,012). As análises multivariadas demostraram que a categoria American Society of Anesthesiologists III/IV e a metástase linfonodal foram fatores significativamente associados à pior sobrevida global. CONCLUSÕES: A quimioterapia pré-operatória foi associada à maior sobrevida no câncer gástrico. Não houve diferença na taxa de complicações pós-operatórias e mortalidade em comparação com a cirurgia inicial.

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning

ABSTRACT Objective To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. Methods This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. Results Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. Conclusion HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Advances in Treatment of Locally Advanced Renal Cell Carcinoma / 肿瘤防治研究

Renal cell carcinoma (RCC) is the third most common malignant tumor of the genitourinary system. During disease progression, RCC can undergo local and/or distant metastasis, which seriously affects the prognosis of the patient. With the advancements in targeted therapy and immunotherapy for advanced RCC, treatment for locally advanced RCC has changed. Studies have focused on applying targeted therapy or immunotherapy in the perioperative period. This article aims to review progress on treatment of locally advanced RCC to offer references for novel treatment strategies.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Application of Neoadjuvant Chemoimmunotherapy in Resectable NSCLC / 中国肺癌杂志

BACKGROUND@#For resectable non-small cell lung cancer (NSCLC), the CheckMate-816 study demonstrated that neoadjuvant chemoimmunotherapy increased the rate of complete pathologic response (pCR) by 21.8% compared with chemotherapy alone and resulted in a significant benefit in event-free survival (EFS). This study aimed to investigate the safety and feasibility of this approach in the real world.@*METHODS@#Clinical data from patients with NSCLC who underwent surgery after neoadjuvant chemoimmunotherapy or chemotherapy alone in two centers were analyzed retrospectively, and subgroup analyses were performed for the chemoimmunotherapy group according to treatment cycle. The primary study endpoints were EFS and major pathologic response (MPR), and the secondary study endpoints were pCR, overall survival (OS), treatment-related adverse events (TRAEs), and surgery-related metrics.@*RESULTS@#As of April 2023, 89 patients had been enrolled, including 54 in the chemoimmunotherapy group and 35 in the chemotherapy alone group. MPR was achieved in 31 (57.4%) and 5 (14.3%) patients in the chemoimmunotherapy group and chemotherapy alone group, respectively (OR=8.09, 95%CI: 2.72-24.04, P<0.001); pCR was achieved in 25 (46.3%) patients in the chemoimmunotherapy group and no patient in the chemotherapy alone group (P<0.001). The median follow-up time was 22.1 months. At 24 months, the EFS rates of the chemoimmunotherapy group and the chemotherapy alone group were 77.0% and 56.7%, respectively (P=0.026), and the OS rates were 87.1% and 67.7%, respectively (P=0.020). In the neoadjuvant chemoimmunotherapy group, there was no significant difference between the 1-2 cycles and 3-5 cycles groups in terms of operation time, intraoperative blood loss, and postoperative complications.@*CONCLUSIONS@#Neoadjuvant chemoimmunotherapy was more effective than chemotherapy alone and did not increase the risk associated with surgery. An increase in the number of cycles of neoadjuvant chemoimmunotherapy had no significant effect on the difficulty of surgery.

Clinical efficacy of neoadjuvant chemotherapy combined with radical surgery for elderly patients with locally advanced gastric cancer / 中华普通外科杂志

Objective:To evaluate the safety and feasibility of neoadjuvant chemotherapy (NACT) combined with radical surgery for elderly patients with locally advanced gastric cancer (LAGC).Methods:One hundred and fourty eight patients with LAGC after NACT and gastrectomy between 2012 and 2020 were retrospectively reviewed. They were divided into two groups: (1) <65 years old (111 cases) and (2) ≥65 years old (37 cases) and their clinicopathological and prognostic data were compared.Results:There was no significant difference between the two groups in the incidence of hematological complications such as anemia ( χ2=0.235, P=0.628), leukopenia ( χ2=0.613, P=0.434), neutropenia ( χ2=0.011, P=0.918) and thrombocytopenia ( χ2=0.253, P=0.615) and non-hematological complications such as nausea ( χ2=0.092, P=0.762), vomiting ( χ2=0.166, P=0.683), diarrhea ( χ2=0.015, P=0.902) and mucositis ( χ2=0.199, P=0.766) due to NACT. There were no statistical differences between the older patients and the younger in operation duration ( t=0.270, P=0.604), intraoperative bleeding ( t=1.140, P=0.250) and R 0 resection rate ( χ2=0.105, P=0.750). The incidence of postoperative complications was 25.2% and 37.8% in the younger patients and the olders ( χ2=2.172, P=0.141). Pleural effusion ( χ2=7.007, P=0.008) and pulmonary infection ( χ2=10.204, P=0.001) was significantly higher in the older patients than in the youngers. The 3-year progression-free survival rate ( t=0.494, P=0.482) and 3-year overall survival rate ( t=0.013, P=0.908) were comparable between the two groups. Conclusions:NACT combined with radical surgery is safe and effective in elderly patients with LAGC, except for higher perioperative pulmonary-related complications.