NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY TRANSHITAL ESOPHAGECTOMY IN LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: IMPACT OF PATHOLOGICAL COMPLETE RESPONSE.

BACKGROUND: Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. AIM: To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. METHODS: Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. RESULTS: The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). CONCLUSIONS: There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.

Neoadjuvant chemoradiotherapy followed by transhital esophagectomy in locally advanced esophageal squamous cell carcinoma: impact of pathological complete response / Quimiorradioterapia neoadjuvante seguido de esofagectomia transhital no carcinoma espinocelular do esôfago avançado: impacto da resposta patológica completa

ABSTRACT Background Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. Aim: To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. Methods: Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. Results The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). Conclusions There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.

RESUMO Racional: A terapia multimodal com quimioradioterapia neoadjuvantes, seguido de esofagectomia tem oferecido melhores resultados de sobrevida, em comparação à esofagectomia isolada, no câncer do esôfago avançado. Além disso, os doentes que apresentam resposta patológica completa ao tratamento neoadjuvante, têm evoluido com maior sobrevida global e maior sobrevida livre de doença em comparação aos que apresentam resposta incompleta. Objetivo: Comparar os resultados de sobrevida global e sobrevida livre de doença entre os doentes com resposta completa e incompleta, submetidos à quimioradioterapia neoadjuvante, com dois esquemas terapêuticos, seguidos de esofagectomia transhiatal. Métodos: Estudo retrospectivo, aprovado pelo Comitê de Ética em pesquisa, analisando os prontuários de 56 doentes, divididos em dois grupos de pacientes, submetidos a radioterapia (4400 a 5400 cGY) e quimioterapia (5-Fluorouracil+Cisplatina versus Paclitaxel+Carboplatina) neoadjuvantes e posteriormente a tratamento cirúrgico, no período de 2005 a 2012, portadores de carcinoma espinocelular do esôfago. Resultados: Os grupos não diferiram significativamente quanto ao gênero, raça, idade, complicações pós-operatórias, sobrevida livre de doença e sobrevida global. A sobrevida em 5 anos de doentes com resposta incompleta e completa foram, respectivamente, 18,92% e 42,10% (p>0,05). Entretanto, os doentes que receberam Paclitaxel+Carboplatina, tiveram melhores respostas patológicas completas à neoadjuvância, em comparação ao 5-Fluorouracil+Cisplatina (47,37% versus 21,62% - p=0,0473, p<0,05). Conclusões: Não houve diferença estatística na sobrevida global e na sobrevida livre de doença dos doentes que apresentaram resposta patológica completa à neoadjuvância. Os doentes submetidos ao esquema terapêutico com Paclitaxel e Carboplastina, mostraram diferença significativa com melhor resposta patológica completa e evolução da doença. Novos parâmetros são indicados para esclarecer o real valor na sobrevida, da resposta patológica completa à neoadjuvância, no câncer de esôfago.

Chemoradiotherapy With or Without Surgery for Esophageal Squamous Cancer According to Hospital Volume.

PURPOSE: Esophageal squamous cell cancer (ESCC) is still associated with a dismal prognosis. However, surgical series have shown that high-volume hospitals have better outcomes and that the impact of center volume on definitive chemoradiotherapy (dCRT) or CRT plus surgery (CRT + S) remains unknown. METHODS: We performed a retrospective analysis of patients with locally advanced stage II-III (non-T4) ESCC treated with dCRT or CRT + S in São Paulo state, Brazil. Descriptive variables were assessed with the χ2 test after categorization of hospital volume (high-volume [HV] center, top 5 higher volume, or low-volume [LV] center). Overall survival (OS) was assessed with Kaplan-Meier curves, log-rank tests, and Cox proportional hazards. Finally, an interaction test between each facility's treatments was performed. RESULTS: Between 2000 and 2013, 1,347 patients were analyzed (77% treated with dCRT and 65.7% in HV centers) with a median follow-up of 23.7 months. The median OS for dCRT was 14.1 months (95% CI, 13.3 to 15.3 months) and for CRT + S, 20.6 months (95% CI, 16.1 to 24.9 months). In the multivariable analysis, dCRT was associated with worse OS (hazard ratio [HR], 1.38; 95% CI, 1.19 to 1.61; P < .001) compared with CRT + S. HV hospitals were associated with better OS (HR, 0.82; 95% CI, 0.71 to 0.94; P = .004) compared with LV hospitals. Importantly, CRT + S superiority was restricted to HV hospitals (dCRT v CRT + S: HR, 1.56; 95% CI, 1.29 to 1.89; P < .001), while in LV hospitals, there was no statistically significant difference (HR, 1.23; 95% CI, 0.88 to 1.43; P = .350), with a significant interaction test (Pinteraction = .035). CONCLUSION: Our data show that CRT + S is superior to dCRT in the treatment of ESCC exclusively in HV hospitals, which favors the literature trend to centralize the treatment of ESCC in HV centers.

Arrabidaea chica for oral mucositis in patients with head and neck cancer: a protocol of a randomised clinical trial.

INTRODUCTION: Oral mucositis is an iatrogenic condition of erythematous inflammatory changes which tends to occur on buccal and labial surfaces, the ventral surface of the tongue, the floor of the mouth and the soft palate of patients receiving chemotherapy. This protocol of ongoing randomised parallel group clinical trial aims to access the therapeutic effect of an herbal gel containing 2.5% Arrabidaea chica Verlot standardised extract on oral mucositis in patients with head and neck cancer compared with low-level laser therapy. METHODS AND ANALYSIS: Patients with head and neck cancer held at Clinics Hospital of University of Campinas, Sao Paulo, who develop early signs/symptoms of oral mucositis are eligible. Baseline characteristics of participants include oral mucositis grade and quality of life assessments. Enrolment started in November 2017 with allocation of patients to one of the study groups by means of randomisation. Patients will be treated either with Arrabidaea chica or laser until wound healing. Monitoring includes daily assessment of mucositis grade and diameter measurement by photographs and millimetre periodontal probe. Treatments will be concluded once mucositis is healed. A blinded assessor will evaluate mucositis cure after referred by the study team. At this point, the gel tube will be weighed to indirectly assess patient's compliance. At close-out, data will be analysed by a blinded researcher following the procedures described in the statistical analyses. ETHICS AND DISSEMINATION: This clinical trial was approved by the ethics committee of research in humans at the Faculty of Medical Sciences of University of Campinas (report no. 1,613,563/2016). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: RBR-5×4397.

Stereotactic radiosurgery for spinal metastases: a literature review.

OBJECTIVE: The spine is the most common location for bone metastases. Since cure is not possible, local control and relief of symptoms is the basis for treatment, which is grounded on the use of conventional radiotherapy. Recently, spinal radiosurgery has been proposed for the local control of spinal metastases, whether as primary or salvage treatment. Consequently, we carried out a literature review in order to analyze the indications, efficacy, and safety of radiosurgery in the treatment of spinal metastases. METHODS: We have reviewed the literature using the PubMed gateway with data from the MEDLINE library on studies related to the use of radiosurgery in treatment of bone metastases in spine. The studies were reviewed by all the authors and classified as to level of evidence, using the criterion defined by Wright. RESULTS: The indications found for radiosurgery were primary control of epidural metastases (evidence level II), myeloma (level III), and metastases known to be poor responders to conventional radiotherapy--melanoma and renal cell carcinoma (level III). Spinal radiosurgery was also proposed for salvage treatment after conventional radiotherapy (level II). There is also some evidence as to the safety and efficacy of radiosurgery in cases of extramedullar and intramedullar intradural metastatic tumors (level III) and after spinal decompression and stabilization surgery. CONCLUSION: Radiosurgery can be used in primary or salvage treatment of spinal metastases, improving local disease control and patient symptoms. It should also be considered as initial treatment for radioresistant tumors, such as melanoma and renal cell carcinoma.

Radiocirurgia estereotáxica para metástases de coluna vertebral: revisão de literatura / Stereotactic radiosurgery for spinal metastases: a literature review

OBJECTIVE: The spine is the most common location for bone metastases. Since cure is not possible, local control and relief of symptoms is the basis for treatment, which is grounded on the use of conventional radiotherapy. Recently, spinal radiosurgery has been proposed for the local control of spinal metastases, whether as primary or salvage treatment. Consequently, we carried out a literature review in order to analyze the indications, efficacy, and safety of radiosurgery in the treatment of spinal metastases. METHODS: We havereviewed the literature using the PubMed gateway with data from the MEDLINE library on studies related to the use of radiosurgery in treatment of bone metastases in spine. The studies were reviewed by all the authors and classified as to level of evidence, using the criterion defined by Wright. RESULTS: The indications found for radiosurgery were primary control of epidural metastases (evidence level II), myeloma (level III), and metastases known to be poor responders to conventional radiotherapy - melanoma and renal cell carcinoma (level III). Spinal radiosurgery was also proposed for salvage treatment after conventional radiotherapy (level II). There is also some evidence as to the safety and efficacy of radiosurgery in cases of extramedullar and intramedullar intradural metastatic tumors (level III) and after spinal decompression and stabilization surgery. CONCLUSION: Radiosurgery can be used in primary or salvage treatment of spinal metastases, improving local disease control and patient symptoms. It should also be considered as initial treatment for radioresistant tumors, such as melanoma and renal cell carcinoma.

OBJETIVO: A coluna vertebral é o local mais comum de metástases ósseas. Uma vez que a cura não pode ser obtida, o controle local e o alívio dos sintomas é a base do tratamento, sendo este fundamentado no uso de radioterapia convencional. Recentemente, a radiocirurgia espinhal foi proposta para o controle local das metástases na coluna, seja como tratamento primário ou de resgate. Dessa forma, realizamos uma revisão da literatura para analisar as indicações, a eficácia e a segurança da radiocirurgia no tratamento das metástases da coluna. MÉTODOS: A revisão de literatura foi realizada no portal PubMed - dados da biblioteca MEDLINE, sobre os estudos relacionados ao uso da radiocirurgia no tratamento para metástases ósseas na coluna vertebral. Os estudos foram revisados por todos os autores e classificados quanto ao nível de evidência, utilizando critério definido por Wright. RESULTADOS: As indicações encontradas para radiocirurgia foram: controle primário de metástases epidurais (nível II de evidência), mieloma (nível III) e metástases sabidamente pouco responsivas à radioterapia convencional - melanoma e carcinoma de células renais - (nível III). A radiocirurgia espinhal também foi proposta para o tratamento de resgate após falha da radioterapia convencional (nível II). Existe ainda alguma evidência quanto à segurança e a eficácia da radiocirurgia em casos de tumores metastáticos intradurais extramedulares e intramedulares (nível III), e após cirurgias de descompressão e estabilização da coluna. CONCLUSÃO: A radiocirurgia, portanto, pode ser usada no tratamento primário ou de resgate de metástases espinhais, melhorando o controle local da doença e dos sintomas dos pacientes. Deve ainda ser considerada como tratamento inicial para tumores radiorresistentes, como melanoma e carcinoma de células renais.