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.

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.

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.

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.

Thoracoscopic laparoscopy-assisted Ivor-Lewis resection of esophagogastric junction cancer / 中华肿瘤杂志

Objective: To investigate the outcome of patients with esophagogastric junction cancer undergoing thoracoscopic laparoscopy-assisted Ivor-Lewis resection. Methods: Eighty-four patients who were diagnosed with esophagogastric junction cancer and underwent Ivor-Lewis resection assisted by thoracoscopic laparoscopy at the National Cancer Center from October 2019 to April 2022 were collected. The neoadjuvant treatment mode, surgical safety and clinicopathological characteristics were analyzed. Results: Siewert type Ⅱ (92.8%) and adenocarcinoma (95.2%) were predominant in the cases. A total of 2 774 lymph nodes were dissected in 84 patients. The average number was 33 per case, and the median was 31. Lymph node metastasis was found in 45 patients, and the lymph node metastasis rate was 53.6% (45/84). The total number of lymph node metastasis was 294, and the degree of lymph node metastasis was 10.6%(294/2 774). Among them, abdominal lymph nodes (100%, 45/45) were more likely to metastasize than thoracic lymph nodes (13.3%, 6/45). Sixty-eight patients received neoadjuvant therapy before surgery, and nine patients achieved pathological complete remission (pCR) (13.2%, 9/68). Eighty-three patients had negative surgical margins and underwent R0 resection (98.8%, 83/84). One patient, the intraoperative frozen pathology suggested resection margin was negative, while vascular tumor thrombus was seen on the postoperative pathological margin, R1 resection was performed (1.2%, 1/84). The average operation time of the 84 patients was 234.5 (199.3, 275.0) minutes, and the intraoperative blood loss was 90 (80, 100) ml. One case of intraoperative blood transfusion, one case of postoperative transfer to ICU ward, two cases of postoperative anastomotic leakage, one case of pleural effusion requiring catheter drainage, one case of small intestinal hernia with 12mm poke hole, no postoperative intestinal obstruction, chyle leakage and other complications were observed. The number of deaths within 30 days after surgery was 0. Number of lymph nodes dissection, operation duration, and intraoperative blood loss were not related to whether neoadjuvant therapy was performed (P>0.05). Preoperative neoadjuvant chemotherapy combined with radiotherapy or immunotherapy was not related to whether postoperative pathology achieved pCR (P>0.05). Conclusion: Laparoscopic-assisted Ivor-Lewis surgery for esophagogastric junction cancer has a low incidence of intraoperative and postoperative complications, high safety, wide range of lymph node dissection, and sufficient margin length, which is worthy of clinical promotion.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Safety and efficacy analysis of hepatic artery infusion chemotherapy combined with immune targeted therapy for single CNLC Ⅰb hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Hot topics in perioperative immune combination therapy for liver cancer / 中华肝胆外科杂志

Most patients with primary hepatocellular carcinoma (HCC) are already in advanced stage when they are diagnosed, with a short survival period and an extremely poor prognosis. HCC seriously threatens the life and health of Chinese people. In recent years, breakthroughs have been made in systemic treatment of HCC, especially in immunotherapy represented by immune checkpoint inhibitors, which has broken the single therapy situation of molecular targeted drugs. And the strategy of immunotherapy combined with anti-angiogenic therapy has shown superiority and profoundly changed the treatment strategy of HCC. This article focuses on several hotspots of immune checkpoint inhibitors combined with anti-angiogenic targeted drugs in the perioperative scenario of HCC, and takes stock of the latest research progress of immunotherapy combined with anti-angiogenic drugs regimens in the perioperative application of HCC.

Research progress on neoadjuvant immunotherapy for esophageal cancer / 中华放射肿瘤学杂志

Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.

The role of radiomics and artificial intelligence in predicting and evaluating the efficacy of neoadjuvant chemoradiotherapy for rectal cancer / 中华放射肿瘤学杂志

Predicting and evaluating the efficacy of neoadjuvant therapy for rectal cancer are of clinical significance and health economic value. At present, exploring the methods of predicting and evaluating the efficacy of neoadjuvant therapy have become research hotspot, focus and difficulty at home and abroad. Radiomics and artificial intelligence (AI) are two rapidly developing technologies. It is worthy of integrating radiomics with AI to build a model for predicting and evaluating the efficacy of neoadjuvant therapy and support individualized clinical decision-making and treatment options. In this article, literature review related to neoadjuvant chemoradiotherapy for rectal cancer based on radiomics and AI was conducted, aiming to explore the prospect and advantages of radiomics and AI in the prediction and evaluation of neoadjuvant therapy.

Exploration of feasible total neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Neoadjuvant radiotherapy and chemotherapy combined with surgery is the standard treatment for patients with locally advanced esophageal cancer, which has been widely applied in clinical practice. Clinical efficacy has also been recognized by clinicians. However, even after the completion of neoadjuvant radiotherapy and subsequent surgical treatment, some patients still have local regional recurrence or distant metastasis in a short period of time. Among them, distant metastasis has become the main failure mode of patients undergoing surgery after neoadjuvant radiotherapy and chemotherapy, indicating that this treatment remains to be further improved. Based on the experience of patients with rectal cancer benefiting from total neoadjuvant therapy, the feasibility and implementation of total neoadjuvant therapy for locally advanced esophageal cancer were discussed in this article.

Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies / 中华放射肿瘤学杂志

Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.

Value of delta radiomic based on contrast enhanced MRI to predict pathological complete response after neoadjuvant therapy for breast cancer / 中华放射学杂志

Objective:To investigate the value of delta radiomics based on longitudinal changes of dynamic contrast enhanced MRI (DCE-MRI) in predicting pathological complete response (pCR) after neoadjuvant therapy (NAT) for breast cancer.Methods:The clinicopathological and imaging data of 117 patients with breast cancer confirmed by surgical pathology from April 2019 to November 2021 at Jiangxi Cancer Hospital were analyzed retrospectively. All patients were female with 23?74 (48±10) years old. The patients were randomly divided into training (81 cases) and test sets (36 cases) at the ratio of 7∶3 according to the number of random seeds in the software. All patients underwent DCE-MRI before and after early NAT (2 courses). The maximum diameter relative regression value of breast tumors before and after early NAT (D%) was calculated and used to construct a conventional imaging model. The delta radiomic features were extracted based on pre-NAT and early-NAT (2 courses) DCE-MRI and selected by redundancy analysis and least absolute shrinkage and selection operator algorithm. A ten-fold cross-validation method was used to construct the delta radiomic model and Radscore was calculated for each patient. All patients were classified into pCR group and non-pCR group according to the surgical pathology after NAT. Significant clinicopathological variables were selected by univariate analysis and stepwise regression method. They were integrated with D% and Radscore to build the combined model and nomogram. The model performance in predicting pCR after NAT in breast cancer was evaluated by the receiver operating characteristic curve and the area under the curve (AUC), and the clinical utility of the models was compared by using clinical decision curves.Results:The combined model had the best diagnostic performance among the three models, with an AUC of 0.90 in the training set and 0.87 in the test set. The Radscore had the highest weight in the nomogram. In the training set, the diagnostic performance of the combined model and delta radiomics model were better than that of the conventional imaging model ( Z=?3.48, P=0.001; Z=2.54, P=0.011). The clinical decision curves showed an overall greater clinical benefit of the combined model compared with the conventional imaging model and delta radiomic model. Conclusions:The addition of significant clinicopathological variables and Radscore of delta radiomic model which represents the longitudinal changes in tumor heterogeneity to the conventional imaging model may improve the predictive ability of pCR. The delta radiomic may serve as a noninvasive biomarker for early prediction of NAT response.