Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

Hotspots and prospects of esophageal cancer research in China / 中华胃肠外科杂志

Esophageal cancer is a malignant tumor with a high incidence in China. At pesent, advanced esophageal cancer patients are still frequently encountered. The primary treatment for resectable advanced esophageal cancer is surgery-based multimodality therapy, including preoperative neoadjuvant therapy, such as chemotherapy, chemoradiotherapy or chemotherapy plus immunotherapy, followed by radical esophagectomy with thoraco-abdominal two-field or cervico-thoraco-abdominal three-field lymphadenectomy via minimally invasive approach or thoracotomy. In addition, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy, or immunotherapy may also be administered if suggested by postoperative pathological results. Although the treatment outcome of esophageal cancer has improved significantly in China, many clinical issues remain controversial. In this article, we summarize the current hotspots and important issues of esophageal cancer in China, including prevention and early diagnosis, treatment selection for early esophageal cancer, surgical approach selection, lymphadenectomy method, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and nutritional support treatment.

Current status and prospects of neoadjuvant therapy for resectable pancreatic cancer / 中华外科杂志

Pancreatic cancer is a highly malignant tumor. About 75% of patients with pancreatic cancer who underwent radical surgical resection will still experience postoperative recurrence. Neoadjuvant therapy could improve outcomes in patients with borderline resectable pancreatic cancer,has become a consensus;however it is still controversial in resectable pancreatic cancer. Limited high-quality randomized controlled trial studies support the routine initiation of neoadjuvant therapy in resectable pancreatic cancer. With the development of new technologies, such as next-generation sequencing, liquid biopsy, imaging omics, and organoids, patients are expected to benefit from the precision screening of potential candidates for neoadjuvant therapy and individualized treatment strategy.

Advances in tumor regression patterns and safe distance of distal resection margin after neoadjuvant therapy for rectal cancer / 中华胃肠外科杂志

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.

Neoadjuvant immunotherapy for colorectal cancer / 中华胃肠外科杂志

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.

Evaluation of lateral lymph node metastasis in mid-low rectal cancer and planning of multi-disciplinary treatment / 中华胃肠外科杂志

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

Neoadjuvant chemotherapy for patients with locally advanced penile cancer: an updated evidence / 亚洲男科学杂志(英文版)

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.

Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.

Supervivencia relacionada con la respuesta patológica, luego de quimioterapia neoadyuvante en cáncer de mama / Survival related to pathological response, after Neoadjuvant Chemotherapy in breast cancer

Quimioterapia neoadyuvante (NAC) en cáncer de mama permite conocer la sensibilidad del tumor al tratamiento, alcanzar respuesta patológica completa (pRC), está asociada a mejor supervivencia en cáncer de mama localmente avanzado. El objetivo de este estudio fue conocer el impacto de la pRC en la supervivencia en una cohorte de pacientes tratadas con NAC y cirugía. Se realizo un estudio de diseño observacional de tipo retrospectivo, correlacional, con un seguimiento promedio de 90 meses, de una cohorte de pacientes tratadas con NAC y cirugía desde enero del 2009 a diciembre del 2011. El análisis de datos se realizó mediante el software estadístico SPSS v22.0, para el análisis de supervivencia se utilizó el método de Kaplan Meier, para comparar supervivencias se consideró significativa una p<0,05. Entre las características principales de 199 pacientes, se destacan: edad joven a la presentación, elevado índice de proliferación y alta frecuencia del tipo inflamatorio. pRC ocurrió en el 14,1% de pacientes y la supervivencia global (SG) de acuerdo con la respuesta patológica se comparó entre aquellas pacientes que obtuvieron pRC, con las que tuvieron enfermedad residual, con una SG del 71,4% vs 45% respectivamente, con una diferencia significativa (p:0.009). En esta cohorte de pacientes la pRC impactó en la supervivencia en todos los subtipos clínico-patológicos, sobre todo en el subtipo triple negativo. Evaluar los datos en el entorno real es importante para definir estrategias y mejorar los resultados.

Neoadjuvant chemotherapy (NAC) in breast cancer allows knowing the sensitivity of the tumor to treatment, achieving pathological response complete (pRC), and is associated with better survival in locally advanced breast cancer. The objective of this study was to determine the impact of pRC on survival in a cohort of patients treated with NAC and surgery. A retrospective, correlational observational design study was carried out, with an average follow-up of 90 months, of a cohort of patients treated with NAC and surgery from January 2009 to December 2011. Data analysis was performed using the software SPSS v22.0 statistic, for the survival analysis the Kaplan Meier method was used, to compare survivals a p <0.05 was considered significant. Among the main characteristics of 199 patients, the following stand out: young age at presentation, high proliferation index and high frequency of the inflammatory type. pRC occurred in 14.1% of patients and overall survival (OS) according to the pathological response was compared between those patients who obtained pRC, with those who had residual disease, with an OS of 71.4% vs 45% respectively, with a significant difference (p: 0.009). In this cohort of patients, pRC impacted on survival in all clinicopathological subtypes, especially in the triple negative subtype. Evaluating data in the real environment is important to define strategies and improve results.

Transarterial radioembolization for liver tumors as neoadjuvant therapy: three case reports / Radioembolização transarterial hepática como terapia neoadjuvante: relato de três casos

ABSTRACT Transarterial radioembolization (TARE) with yttrium-90 microspheres is a palliative locoregional treatment, minimally invasive for liver tumors. The neoadjuvant aim of this treatment is still controversial, however, selected cases with lesions initially considered unresectable have been enframed as candidates for curative therapy after hepatic transarterial radioembolization. We report three cases in which the hepatic transarterial radioembolization was used as neoadjuvant therapy in an effective way, allowing posterior potentially curative therapies.

RESUMO A radioembolização transarterial hepática com microesferas de ítrio-90 é uma modalidade paliativa de tratamento locorregional minimamente invasiva. O objetivo neoadjuvante deste tratamento ainda é controverso, mas casos selecionados de lesões consideradas inicialmente irressecáveis reenquadram-se como candidatos à terapia curativa após a radioembolização transarterial hepática. Relatamos três casos em que a radioembolização transarterial hepática foi utilizada como terapia neoadjuvante de forma efetiva possibilitando aplicação posterior de terapias potencialmente curativas.

Hormone receptor-negative as a predictive factor for pathologic complete response to neoadjuvant therapy in breast cancer / Receptor hormonal negativo como fator preditivo para resposta patológica completa ao tratamento neoadjuvante de câncer de mama

ABSTRACT Objective To define a predictive factor for pathologic complete response, compare the oncologic outcomes associated with the degree of pathologic response after neoadjuvant chemotherapy, and to analyze pathologic complete response as a prognostic factor for overall survival and progression-free survival. Methods A retrospective study of patients admitted to Hospital Estadual Mário Covas and Hospital Anchieta from 2008 to 2012, with locally advanced breast cancer. Hormone receptor status, HER2 status, histologic and nuclear grade, age upon diagnosis and histological type of the tumor were analyzed. Pathologic evaluation of the tumor was subdivided into pathologic complete response, defined by the absence of tumor; intermediate response, considered as a favorable stage; and poor response, considering low-responder patients. Data obtained were submitted to statistical analysis. Results The study included 243 patients. There was an association of pathologic complete response with HER-2 negative, histological grade 3, stage III, hormone receptor negative, positive lymph node, older age and more advanced tumors. However, after multivariate analysis the only predictor of pathologic complete response was the presence of negative hormone receptor. By analyzing the prognostic factors, hormone receptor negative was considered as an independent risk factor, and pathologic complete response was considered as an independent protective factor. Conclusion Hormone receptor negative is predictive of pathologic complete response and is an isolated risk factor for lower progression-free survival and overall survival. Pathologic complete response is a protective factor for these same survival analyses.

RESUMO Objetivo Definir um fator preditivo para resposta patológica completa, comparar os resultados oncológicos associados com o grau de resposta patológica, após quimioterapia neoadjuvante, e analisar a resposta patológica completa como fator prognóstico para sobrevivência global e livre de progressão de doença. Métodos Estudo retrospectivo de pacientes admitidas no Hospital Estadual Mário Covas e Hospital Anchieta, no período de 2008 a 2012, com câncer de mama localmente avançado. Foram utilizados status dos receptores hormonais, proteína HER2, grau histológico e nuclear, idade do paciente ao diagnóstico e tipo histológico do tumor. A avaliação patológica do tumor foi subdividida em resposta patológica completa, definida com ausência de tumor; resposta intermediária, considerada como um estádio favorável; e resposta ruim, considerando os pacientes pouco respondedores. As informações obtidas foram submetidas à análise estatística. Resultados Foram incluídas 243 pacientes. Verificou-se associação de resposta patológica completa entre HER-2 negativo, grau histológico 3, estadiamento III, receptor hormonal negativo, linfonodo positivo, maior idade e tumores mais avançados. Porém, após análise multivariada, o único fator preditivo de resposta patológica completa foi presença de receptor hormonal negativo. Ao analisar fatores prognósticos, receptor hormonal negativo permaneceu como variável independente de risco, e resposta patológica completa, como variável independente de proteção. Conclusão O receptor hormonal negativo é fator preditivo isolado de resposta patológica completa e fator de risco para menor sobrevida livre de doença e sobrevida global. Já a resposta patológica completa é fator protetor para estas mesmas análises de sobrevivência.

Modificación del abordaje quirúrgico en tumores estromales gástricos posterior a neoadyuvancia con Imatinib / Change of surgical approach in gastrointestinal stromal tumors after neoadyuvant therapy with Imatinib

Resumen Introducción: El tratamiento de los tumores estromales gastrointestinales (GIST) de alto riesgo es quirúrgico. Su resultado podría variar al usarse neoadyuvancia. Objetivo: Evaluar si el uso de la terapia neoadyuvante con imatinib puede cambiar el abordaje quirúrgico en los tumores estromales gastrointestinales de alto riesgo. Materiales y Métodos: Se realizó un análisis retrospectivo en el Hospital Clínic de Barcelona entre enero de 2002 y mayo de 2016. Resultados: Se obtuvo un total de 8 pacientes. La edad media fue 66,1 ± 13,3 años. La ubicación del tumor fue de 37,5% (3) en el tercio superior, el 50% (4) en el tercio medio y el 12,5% (1) en el tercio inferior. Debido a la clasificación de riesgo alto, la ubicación y/o la necesidad de resecciones multiviscerales, se indicó, previa evaluación comité oncológico, realizar terapia neoadyuvante. La mediana de tiempo de neoadyuvancia fue de 30 semanas. En el 100% (8) de los casos se logró un cambio de enfoque quirúrgico después de la utilización de imatinib. En todos los casos se realizó un resección local (7 laparoscópica y 1 endolaparoscópica) con márgenes negativos La biopsia posoperatoria mostró un promedio de 51,2% de reducción del tamaño tumoral inicial, lo que resultó en una diferencia estadística (p < 0,01) con el tamaño inicial de las lesiones. Durante el seguimiento, tanto la sobrevida relacionada al tumor como la global, fue de un 100%. Conclusión: La terapia neoadyuvante podría cambiar el abordaje quirúrgico de los pacientes con GIST gástrico de riesgo intermedio o alto mediante la reducción del tamaño tumoral, permitiendo realizar cirugías más económicas y logrando resultados oncológicos adecuados.

Introduction: The treatment of high-risk gastrointestinal stromal tumors (GIST) is surgical. Results may change when using neoadjuvant. Objetive: To evaluated if the use of neoadjuvant therapy with imatinib can change the surgical approach in high risk gastrointestinal stromal tumors (GIST). Materials and Methods: A retrospective analysis was performed from a prospective collected database in Hospital Clinic of Barcelona between January 2002 and May 2016. Results: A total of 8 patients were analyzed with a mean age of 66.1 ± 13.3 years. The tumor location was upper third 37.5% (3) cases, 50% (4) in the middle third and 12.5% (1) in lower third. Because of high risk classification, location and the need of multivisceral resections, neoadjuvant therapy was indicated. The median time of neoadjuvant therapy was 30 weeks. In 87.5% (7) cases a change of surgical approach was achieved after the use of imatinib. In 100% of our series laparoscopic wedge resection was performed achieving negative margins of resection. The postoperative biopsy showed 51.2% of reduction of initial tumor size, resulting in statistical difference (p < 0.01). All patients are alive and 100% of tumor related survival was achieved. Conclusion: Neoadjuvant therapy maybe can change the surgical approach of patients with high-intermediate risk gastric GIST by reducing tumor size. This response also eventually can achieve optimal oncological outcome.

Oncological outcomes in extended time intervals between preoperative chemoradiotherapy with capecitabine and surgery in operable rectal adenocarcinoma / Resultados oncológicos en intervalos extendidos de tiempo entre quimioradioterapia preoperatoria con capecitabina y cirugía en adenocarcinoma rectal operable

Objective: To assess whether extended time intervals (8-12, 13-20 and >20 weeks) between the end of neoadjuvant chemoradiotherapy and surgery affect overall survival, disease-free survival. Materials and methods: Retrospective study in 120 patients with rectal adenocarcinoma without evidence of metastasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant chemoradiotherapy with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at the National Cancer Institute of Peru. Dates were evaluated by Kaplan-Meier method, log- rank test and Cox regression analysis. Results: Of the 120 patients, 70 were women (58%). The median age was 63(26-85) years. All received neoadjuvant chemoradiotherapy. No significant difference was found between the association of the median radial (0.6, 0.7 and 0.8 cm; p=0.826) and distal edge (3.0, 3.5 and 4.0 cm; p=0.606) with time interval groups and similarly the mean resected (18.8, 19.1 and 16.0; p=0.239) and infiltrated nodules (1.05, 1.29 and 0.41); p=0.585). The median follow-up time of overall survival and desease free survival was 40 and 37 months, respectively. No significant differences were observed in overall survival (79.0%, 74.6% and 71.1%; p=0.66) and disease-free survival (73.7%, 68.1% and 73.6%; p=0.922) according to the three groups studied at the 3-year of follow-up. Conclusions: We found that widening the time intervals between the end of neoadjuvant chemoradiotherapy and surgery at 24 weeks does not affect the overall survival, disease-free survival and pathological outcomes. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery

Objetivo: Evaluar si los intervalos de tiempo extendidos (8-12, 13-20 y >20 semanas) entre el fin de la quimioradioterapia neoadyuvante y la cirugía afectan la sobrevida global, y la sobrevida libre de enfermedad. Material y métodos: Estudio retrospectivo de 120 pacientes con adenocarcinoma rectal sin evidencia de metástasis (T1-4/N0-2/M0) al momento del diagnóstico que se sometieron a cirugía con intención curativa luego de quimioradioterapia neoadyuvante con capecitabina y tuvieron resección R0 o R1 entre enero 2010 y diciembre 2014 en el Instituto Nacioanal de Enfermedades Neoplásicas de Perú. El análisis se hizo con el método de Kaplan-Meier, la prueba log-rank y la regresión de Cox. Resultados: De 120 pacientes, 70 fueron mujeres (58%). La mediana de la edad fue 63 años (26-85 años). Todos recibieron quimioradioterapia neoadyuvante. No hubo diferencia significativa entre la asociación de las medianas de los bordes radial (0,6, 0.7 y 0,8 cm; p=0,826) y distal (3,0, 3,5 y 4,0 cm; p=0,606) con los intervalos de tiempo de los grupos y similarmente con la media de los ganglios resecados (18,8, 19,1 y 16,0; p=0,239) e infiltrados (1,05, 1,29 y 0,41; p=0,585). No se observaron diferencias significativas en sobrevida global (79,0%, 74,6% y 71,1%; p=0,66) y sobrevida libre de enfermedad (73,7%, 68,1% y 73,6%; p=0,922), en los tres grupos estudiados a 3 años de seguimiento. Conclusiones: Encontramos que aumentar los intervalos de tiempo entre el fin de la quimioradioterapia neoadyuvante y la cirugía hasta 24 semanas no afecta la sobrevida global, sobrevida libre de enfermedad ni los desenlaces patológicos. Esto permitiría extender los intervalos de tiempo en estudios futuros para definir el mejor intervalo de tiempo para la cirugía

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer? / Individualização na segmentação tumoral de imagens de 18F-FDG PET/CT: a chave para avaliação de resposta terapêutica neoadjuvante em pacientes com câncer retal?

Summary Introduction: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. Method: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. Results: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. Conclusion: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Resumo Introdução: O câncer retal (RC) é uma doença de importância global, e o tratamento padrão para o câncer retal localmente avançado compreende quimiorradiação neoadjuvante seguida de cirurgia radical. Independentemente do uso extensivo da captação tumoral mais intensa do 18F-FDG (conhecida como SUVmax) como representativo do consumo glicolítico do tumor nas imagens de PET, há uma tendência para aplicar volume metabólico. Dessa forma, o objetivo do presente estudo foi avaliar um método não invasivo de segmentação tumoral utilizando a 18F-FDG PET para predizer a resposta à quimiorradioterapia neoadjuvante em pacientes com câncer de reto. Método: A amostra consistiu em pacientes com câncer retal em estádios II e III submetidos ao exame de 18F-FDG PET/CT antes e oito semanas após a terapia neoadjuvante. Foi aplicada uma metodologia de segmentação tumoral individualizada para gerar volumes tumorais (SUV2SD). A resposta terapêutica foi avaliada nos espécimes ressecados utilizando as recomendações do protocolo de Dworak. Várias variáveis foram geradas e comparadas com os resultados histopatológicos. Resultados: Dezessete (17) pacientes foram incluídos e analisados. Foram observadas diferenças significativas entre os respondedores (Dworak 3 e 4) e não respondedores para SUVmax-2 (p<0,01), SUV2SD-2 (p<0,05), SUV40%-2 (p<0,05), SUV50%-2 (p<0,05) e SUV60%-2 (p< 0,05). As análises ROC mostraram áreas significativas sob a curva (p<0,01) para a metodologia proposta, com sensibilidade e especificidade variando de 60% a 83% e 73% a 82%, respectivamente. Conclusão: O presente estudo confirmou o poder preditivo das variáveis utilizando uma metodologia não invasiva individualizada para segmentação tumoral baseada em imagens 18F-FDG PET/CT para avaliação da resposta em pacientes com câncer retal após tratamento com quimiorradiação neoadjuvante.

Intraoperative imprint cytology versus histological diagnosis for the detection of sentinel lymph nodes in breast cancer treated with neoadjuvant chemotherapy

OBJECTIVES: To compare imprint cytology and paraffin section histology for sentinel lymph node detection in women with breast cancer treated with neoadjuvant chemotherapy. METHOD: A cross-sectional study and report of the sentinel lymph node statuses of 64 patients with breast cancer who underwent intraoperative imprint cytology and neoadjuvant chemotherapy in a referral cancer institute in Rio de Janeiro, Brazil, between 2014 and 2016. RESULTS: The mean age was 51 years. The most common histological type was invasive ductal carcinoma (93.75%), and the most common differentiation grade was 2 (62.5%). Overall, 153 lymph nodes were identified, with a mean of 2.39/case. Thirty-four lymph nodes tested positive for malignancy by imprint cytology, and 55 tested positive by histology. Of the 55 positive lymph nodes, 41 (74.5%) involved macrometastases, and 14 (25.5%) involved micrometastases. There were 21 false negatives with imprint cytology, namely, 7 for macrometastases and 14 for micrometastases, resulting in a rate of 17.6%. The sensitivity of imprint cytology was 61.8%, with a specificity and positive predictive value of 100%, a negative predictive value of 82.4% and an accuracy of 86.3%. The method presented null sensitivity for the identification of micrometastases. CONCLUSIONS: The false-negative rate with imprint cytology was associated with the number of sentinel lymph nodes obtained. The rate found for complete response to neoadjuvant chemotherapy was comparable to the rates reported in the literature. The accuracy of imprint cytology was good, and its specificity was excellent for sentinel lymph node detection; however, the method was unable to detect lymph node micrometastases.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review / Abordagem multidisciplinar em hormonioterapia neoadjuvante no câncer de mama: uma revisão

ABSTRACT Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HRþ) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemo-therapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2þ) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HRþ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.

RESUMO O câncer de mama é o mais comum, e a principal causa de mortalidade por câncer em mulheres de todo o mundo. Os tumores com receptor hormonal (RH) positivo representam o tipo mais comum desta doença. O benefício e as taxas de resposta à quimioterapia neoadjuvante variam de acordo com a expressão de RH, sendo mais baixa nos tumores luminais em comparação com tumores HER2 positivos ou triplo-negativos. A hormonioterapia neoadjuvante, uma opção para pacientes selecionados com tumores RH positivo localmente avançados, apresenta melhor perfil de tolerabilidade e segurança, e está associada com benefícios adicionais, como baixo custo e fácil acesso. Estes fatores são relevantes, uma vez que 70% das mortes por câncer de mama acontecem em mulheres de países pobres ou em desenvolvimento. Além disso, a hormonioterapia neoadjuvante vem sendo explorada como uma ferramenta científica, ao possibilitar o estudo de biomarcadores que podem predizer desfechos tanto para pacientes individuais quanto para ensaios clínicos em adjuvância. Este artigo de revisão detalha o conhecimento atual e as evidências mais relevantes sobre hormonioterapia neoadjuvante em câncer de mama, assim como perspectivas futuras nesta área.

Neoadjuvant therapy and surgery for rectal cancer. Comparative study between partial and complete pathological response / Terapia neoadjuvante e cirurgia para câncer do reto. Estudo comparativo entre resposta patológica parcial e completa

ABSTRACT Background The approach of locally advanced extra-peritoneal rectal adenocarcinoma implies a treatment with neoadjuvant chemoradiotherapy associated with total mesorectal excision surgery. However, the tumors respond variably to this neoadjuvant therapy, and the mechanisms for response are not completely understood. Objective Evaluate the variables related to the complete tumor response and the outcomes of patients who underwent surgery, comparing those with partial tumor regression and those with total remission of rectal lesion, at the pathological examination. Methods Retrospective analysis of medical records of 212 patients operated between 2000 and 2010, in which 182 (85.9%) obtained partial remission at neoadjuvant therapy (Group 1) and 30 (14.1%), total remission (Group 2). Results No difference was found between the groups in relation to gender, ethnicity, age, tumor distance from the anal verge, occurrence of metastases and synchronous lesions on preoperative staging, dose of radiotherapy and performed surgery. In Group 2, was verified high rate of complete remission when the time to surgery after neoadjuvant therapy was equal or less than 8 weeks (P=0.027), and a tendency of lower levels of pretreatment carcinoembryonic antigen (P=0.067). In pathological analysis, the Group 1 presented in relation to Group 2, more affected lymph nodes (average 1.9 and 0.5 respectively; P=0.003), more angiolymphatic (19.2% and 3.3%; P=0.032) and perineural involvement (15.4% and 0%; P=0.017) and greater number of lymph nodes examined (16.3 and 13.6; P=0.023). In the late follow-up, Group 1 also had lower overall survival than Group 2 (94.1 months and 136.4 months respectively; P=0.02) and disease-free survival (85.5 months and 134.6 months; P=0.004). There was no statistical difference between Group 2 and Group 1 in local recurrence (15% and 3.4%, respectively) and distant metastasis (28% and 13.8%, respectively). Conclusion In this study, the only factor associated with complete remission of rectal adenocarcinoma was the time between neoadjuvant therapy and surgery. This group of patients had less affected lymph nodes, less angiolymphatic and perineural involvement, a longer overall and disease-free survival, but no significant statistical difference was observed in local recurrence and distant metastasis. Although the complete pathologic remission was associated with better prognosis, this not implied in the cure of the disease for all patients.

RESUMO Contexto A abordagem do câncer retal extra-peritoneal localmente avançado implica em um tratamento com quimio e radioterapia neoadjuvante associada com a cirurgia de excisão total do mesorreto. Entretanto, os tumores respondem de maneiras variadas a esta terapia neoadjuvante, não se conhecendo completamente os mecanismos envolvidos nesta resposta. Objetivo Avaliar os fatores relacionados à resposta tumoral completa e o seguimento de pacientes operados, comparando o grupo com regressão parcial com aqueles em que se evidenciou remissão total da lesão no reto, pelo estudo anatomopatológico. Métodos Análise retrospectiva de prontuários médicos de 212 pacientes operados entre 2000 e 2010, sendo que 182 (85,9%) apresentaram remissão parcial a neoadjuvância (Grupo 1) e 30 (14,1%), remissão total (Grupo 2). Resultados Não foi encontrada diferença entre os grupos em relação a gênero, etnia, idade, distância do tumor a margem anal, ocorrência de metástases e lesões sincrônicas no estadiamento pré-operatório, dose de radioterapia e tipo de cirurgia realizada. No Grupo 2, foi verificada alta taxa de remissão completa quando o paciente foi operado com intervalo menor ou igual a 8 semanas após a terapia neoadjuvante (P=0,027), e uma tendência a menor valor de antígeno carcinoembrionário pré-tratamento (P=0,067). Na análise patológica, o Grupo 1 apresentou em relação ao Grupo 2, mais linfonodos acometidos (média de 1,9 e 0,5 respectivamente; P=0,003), mais invasão angiolinfática (19,2% e 3,3%; P=0,032) e perineural (15,4% e 0%; P=0,017), e maior número de linfonodos examinados (16,3 e 13,6; P=0,023). No seguimento tardio, o Grupo 1 também apresentou menor sobrevida global do que o Grupo 2 (94,1 e 136,4 meses, respectivamente; P=0,02) e sobrevida livre de doença (85,5 e 134,6 meses; P=0,004). Não houve diferença estatística entre os Grupo 1 e Grupo 2 na ocorrência de recidiva local (3,4% e 15%, respectivamente; P=0,32) e metástases à distância (13,8 e 28%; P=0,26). Conclusão Neste estudo, o único fator que foi associado à remissão completa do adenocarcimona retal, foi o tempo entre neoadjuvância e a cirurgia. Este grupo de pacientes apresentou menos linfonodos acometidos, menor invasão angiolinfática e perineural, maior sobrevida global e livre de doença, porém não apresentou diferença estatística significativa com relação à recorrência local e metástases à distância. Embora a remissão completa fosse associada com melhor prognóstico, não implicou na cura da doença em todos os pacientes.

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.