Pathologic complete response (ypt0 ypn0) after chemotherapy and radiotherapy neoadjuvant followed by esophagectomy in the squamous cell carcinoma of the esophagus / Resposta patológica completa (ypt0 ypn0) após quimioterapia e radioterapia neoadjuvantes seguido de esofagectomia no carcinoma epidermóide avançado do esôfago: resultados e sobrevida

ABSTRACT Background: Esophageal squamous cell carcinoma is an aggressive neoplasia that requires a multidisciplinary treatment in which survival and prognosis are still not satisfactory. The complete pathologic response to neoadjuvant chemotherapy and radiotherapy is considered a good prognosis factor, and esophagectomy is indicated. Aim: Survival analysis of cases with pathologic complete response (ypT0 ypN0) to neoadjuvant chemotherapy and/or radiotherapy, submmitted to esophagectomy. Methods: Between 1983-2014, 222 esophagectomies were performed, and 177 were conducted to neoadjuvant treatment. In 34 patients the pathologic response was considered complete. Medical records of the patients were retrospectively reviewed regarding type of chemotherapy applied, amount of radiotherapy, interval between the neoadjuvant therapy and the surgery, body mass index; postoperative complications; hospital admission time and survival. Results: The average age was 55.8 years. Twenty-five patients were subjected to chemotherapy and radiotherapy, and nine to neoadjuvant radiotherapy. The total radiation dose ranged from 4400 until 5400 cGy. The chemotherapy was performed with 5FU, cisplatin, and carbotaxol, concomitantly with the radiotherapy. The esophagectomy was transmediastinal, followed by the cervical esophagogastroplasty performed on a average of 49.4 days after the neoadjuvant therapy. The hospital admission time was an average of 14.8 days. During the follow-up period, 52% of the patients submitted to radiotherapy and chemotherapy were disease-free, with 23.6% of them presenting more than five years survival. Conclusions: The neoadjuvant treatment followed by esophagectomy in patients with pathologic complete response is beneficial for the survival of patients with esophageal squamous cell carcinoma.

RESUMO Racional: O carcinoma epidermoide do esôfago é neoplasia de natureza agressiva, que requer tratamento multidisciplinar e tem taxas de sobrevida e prognóstico ainda não satisfatórios. A resposta patológica completa à neoadjuvância com quimioterapia e radioterapia é considerada fator de bom prognóstico e a esofagectomia está indicada. Objetivo: Análise de sobrevida dos casos com resposta patológica completa (ypT0 ypN0) à neoadjuvância com quimioterapia e/ou radioterapia, submetidos à esofagectomia. Métodos: Entre 1983-2014, 222 esofagectomias foram realizadas e 177 foram submetidas ao tratamento neoadjuvante. Em 34 pacientes, a resposta patológica foi considerada completa. Os prontuários dos pacientes foram revisados retrospectivamente quanto ao tipo de quimioterapia aplicada, quantidade de radioterapia, intervalo entre a terapia neoadjuvante e a operação, índice de massa corporal (IMC), complicações pós-operatórias, tempo de internação hospitalar e sobrevida. Resultados: A idade média foi de 55,8 anos. Vinte e cinco pacientes foram submetidos a quimioterapia e radioterapia e nove à radioterapia neoadjuvante. A dose total de radiação variou de 4400 até 5400 cGy. A quimioterapia foi realizada com 5FU, cisplatina e carbotaxol, concomitantemente à radioterapia. A esofagectomia foi transmediastinal, seguida da esofagogastroplastia cervical realizada em média 49,4 dias após a terapia neoadjuvante. O tempo de internação hospitalar foi em média de 14,8 dias. Durante o período de seguimento, 52% dos pacientes submetidos a radioterapia e quimioterapia estavam livres de doença, com 23,6% apresentando sobrevida maior que cinco anos. Conclusão: O tratamento neoadjuvante seguido de esofagectomia, nos pacientes com resposta patológica completa, oferece benefícios na sobrevida de portadores de carcinoma epidermoide do esôfago.

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.

Transanal endoscopic operation for rectal cancer after neoadjuvant therapy

PURPOSE: In this paper we report the oncological outcomes from clinical series of patients with rectal cancer submitted to local excision after neoadjuvant therapy and discuss the indications for local excision in partial clinical responders. METHODS: We analysed a prospective database of 39 patients submitted to a transanal endoscopic operation for rectal cancer after neoadjuvant chemoradiation between 2006 and 2015, comparing clinical and pathological variables, perioperative complications, recurrence rate and overall survival. RESULTS: We obtained 15.4% ypT0, 17.9% ypT1, 35.9% ypT2 and 28.2% ypT3. After a median follow-up of 24 months, tumoral recurrence was observed in 4 patients, one of them with isolated pulmonary metastasis. R0 resection was achieved in 79.5%, and postoperative complications were observed in 30.2% patients and no perioperative mortality occur. Compromise surgical margins do not affect recurrence rate, and 94.9% of patients are alive nowadays. CONCLUSION: Local excision could be associated with low recurrence rate and good overall survival. Short hospitalization time and low level of serious complications observed could be an interesting option for patients who would not tolerate a radical procedure or for those who declined a total mesorectal excision. A strict long-term follow-up must be warranted to detect early tumoral recurrence.