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.

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.

Clinical and pathological characteristics of small cell carcinoma of bladder and the efficacy of neoadjuvant therapy / 现代泌尿外科杂志

【Objective】 To investigate the clinical characteristics and prognostic factors of small cell carcinoma of bladder (SCCB), and to explore the efficacy of neoadjuvant therapy. 【Methods】 Clinical information of 47 SCCB patients were retrospectively collected, and the clinical and pathological features were compared with those of urothelial carcinoma (UBC). The prognostic factors and efficacy of neoadjuvant therapy were also investigated. 【Results】 SCCB had higher baseline tumor staging, and was more likely to invade the muscle (100%) and metastasize distantly (21.3%). The overall survival was poor (median: 13.1 months, 1-year survival rate: 53.7%, 5-year overall survival rate: 15.4%). Tumor T staging was a risk factor for SCCB, while neoadjuvant therapy was an independent protective factor that significantly reduced the risk of recurrence and metastasis (HR: 0.189, 95%CI: 0.051-0.697, P=0.012) and death (HR: 0.177, 95%CI: 0.045-0.698, P=0.013), and significantly improved disease-free survival and overall survival. In addition, compared with neoadjuvant chemotherapy alone, neoadjuvant chemotherapy combined with immunotherapy could improve the pathological complete response rate. 【Conclusion】 SCCB is highly malignant and prone to metastasis, and has a poor prognosis. Neoadjuvant therapy combined with radical cystectomy is recommended as the first-line treatment.

Progress of neoadjuvant therapy for high-risk prostate cancer in the era of novel hormonal therapy / 现代泌尿外科杂志

In the past, the use of neoadjuvant androgen deprivation therapy (ADT) for prostate cancer did not exhibit survival benefits and was not recommended by the practicing guidelines. In recent years, with the emergence of novel hormonal therapeutics such as Abiraterone, Enzalutamide, Apalutamide and Darolutamide, the interest for neoadjuvant therapy has been reignited. Here, we summarize the four categories of neoadjuvant therapy with new hormonal agents, and discuss how to evaluate the efficacy and explore the molecular mechanism after neoadjuvant therapy.

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.

Pathologic assessment of esophageal cancer following neoadjuvant therapy / 中国胸心血管外科临床杂志

@#China is a country with a high incidence of esophageal cancer. Most patients are already in the locally advanced stage when first diagnosed. Preoperative neoadjuvant therapy followed by surgery has become the standard treatment mode for them. Closely related to prognosis, the evaluation of tumor response is essential. Response evaluation criteria in solid tumors is the gold standard to evaluate tumor response, but the lesions must meet the measurement standards. Tumor regression grading (TRG) systems are designed to classify regressive changes after neoadjuvant treatment based on histopathological results to reveal prognostic information. Concentrating on pathologic assessment of esophageal cancer following neoadjuvant therapy, this article reviews histopathological changes, commonly used TRG systems and current debate.

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.

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.

Neoadjuvant immune checkpoint inhibitor therapy and chemotherapy improve pulmonary ventilation and diffusion function in patients with lung cancer / 浙江大学学报·医学版

OBJECTIVES@#To investigate changes of pulmonary ventilation function and diffusion function in lung cancer patients after neoadjuvant immune checkpoint inhibitors (ICIs) therapy combined with chemotherapy treatment.@*METHODS@#Patients with newly diagnosed lung cancer (Ⅱa-Ⅲb) admitted to Zhejiang Cancer Hospital from October 2021 to July 2022, who received ICIs combined with chemotherapy for more than two courses were enrolled. Patients underwent pulmonary ventilation function and diffusion function assessments before and after treatment. The demographic information, sizes and locations of cancer lesions, doses and duration of ICIs used, pulmonary function results before and after treatment, and the tumor regression were documented. The changes of pulmonary function parameters before and after the treatment were analyzed with paired t test and Wilcoxon rank-sum test. The factors influencing the pulmonary function changes were analyzed by multiple linear Lasso regression and ridge regression.@*RESULTS@#Among the 52 patients, 50 cases were males (96.15%) and 43 cases were squamous carcinoma (82.69%). The medium age of the patients was 67 years. After neoadjuvant therapy, 36 patients (69.23%) showed remission of tumor lesions. After treatment, the parameters of pulmonary ventilation inspiratory vital capacity (IVC) and the area under the expiratory flow-volume curve (AREAex), and the parameter of pulmonary diffusion total lung capacity increased compared with the baseline (all P<0.05). Forced vital capacity (FVC) and forced expiratory volume in first second (FEV1) also showed an increasing trend. Multivariate linear Lasso regression and ridge regression showed that baseline IVC had a significant negative effect on IVC improvement (Beta=－0.435, t=－2.968, P<0.01), baseline TLC had a significant negative effect on the improvement of TLC (Beta=－0.266, t=－2.474, P<0.05), and the remission of obstructive pneumonia favored the improvement of TLC (Beta=0.308, t=2.443, P<0.05).@*CONCLUSIONS@#After ICIs neoadjuvant treatment combined with chemotherapy, the lung ventilation and diffusion function can be improved in lung cancer patients, particularly for those with reduced baseline ventilation and diffusion function.

Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC / 中国肺癌杂志

BACKGROUND@#Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients.@*METHODS@#66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored.@*RESULTS@#The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life.@*CONCLUSIONS@#Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.

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)