Conversion therapy for gastric cancer: expanding the treatment possibilities / Terapia de conversão no câncer gástrico: ampliando as possibilidades de tratamento

ABSTRACT Background: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. Aim: To evaluate the results of conversion therapy in the treatment of GC. Methods: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. Results: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. Conclusion: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.

RESUMO Racional : A terapia de conversão no câncer gástrico (CG) é definida como o uso de quimio/radioterapia seguida de ressecção cirúrgica com intenção curativa de um tumor que era considerado irressecável ou oncologicamente incurável. Objetivo : Avaliar os resultados da terapia de conversão no tratamento do CG. Métodos : Análise retrospectiva de todas as operações de CG entre 2009 e 2018. Os pacientes que receberam alguma terapia antes da operação foram também identificados para definir o grupo de conversão. Resultados : Entre 1003 operações realizadas para o CG, 113 foram submetidos ao tratamento neoadjuvante e 16 (1,6%) considerados como terapia de conversão. As principais indicações para o tratamento foram: lesões T4b (n=10), metástase linfonodal (n=4), carcinomatose peritoneal e metástase hepática em 1 caso cada. O diagnóstico foi feito por exame de imagem em 14 casos (75%) e durante o procedimento cirúrgico em 4 casos (25%). Os esquemas quimioterápicos mais utilizados foram XP e mFLOX. Complicações cirúrgicas maiores ocorreram em 4 casos (25%) e 1 (6,3%) foi a óbito. Após seguimento médio de 20 meses, 11 pacientes (68,7%) apresentaram recidiva e 9 (56,3%) morreram. Sobrevida livre de recidiva prolongada acima de 40 meses ocorreu em dois casos. Conclusão : A terapia de conversão pode oferecer possibilidade de sobrevida prolongada para um grupo de pacientes com CG considerados inicialmente fora das possibilidades terapêuticas.

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.

Resultados del tratamiento del cáncer de mama, Programa Nacional de Cáncer del Adulto / Impact of the Chilean Explicit Guaranties Health System (GES) on breast cancer treatment

Background Breast cancer is the most common malignant tumor in women in the world. In 2005, it was incorporated to the Explicit Guaranties Health System (GES) in Chile. Aim To describe the demographic and clinical characteristics of breast cancer patients and to determine the effect of incorporating these women to GES. Material and Methods Medical records of 5,119 women with breast cancer aged 59 ± 14 years, attended at six public hospitals between 2000 and 2010 were reviewed. Median follow up was 87 months (range 1-182). Mortality was assessed using death certificates obtained at the National Identification Registry. Results Sixty six percent of women were in stage I-II, 29% in stage III and 5% in stage IV. Surgery was performed in 4023/5119 cases (79%), adyuvant radiotherapy in 3627/4517 cases (80%), chemotherapy in 3,204/3,424 cases (94%) and hormone therapy in 1,695/2,375 cases (71%). Between 2000 and 2010, there was a significant increase in the proportion of cases in stage I, from 8% to 25%, (p < 0.01). Overall survival (OS) increased 1% per year, since the beginning of GES system (p = 0.024). Five year OS was 75.1%. The figures for Stage I, II, III and IV were 93, 84, 62 and 27% respectively (p < 0.01). Patients without lymph node involvement and who were not triple negative, had a significantly better OS. Conclusions There was a significant increase in stage I cases, and a 1% per year OS improvement after GES system started, compared with the previous period.

Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma

OBJECTIVE: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma. METHODS: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan–Meier method and then compared using the log-rank test. RESULTS: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001). CONCLUSIONS: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response ...

Surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy / Tratamento cirúrgico do câncer de endométrio em estágio clínico precoce sem linfadenectomia radical.

Objective: the main aim of this study was to describe the authors’ experience with the surgical treatment of endometrial cancer without systematic lymphadenectomy. Methods: a retrospective cohort study was carried out on a subset of patients suffering of clinically early-stage endometrial carcinoma who underwent hysterectomy and salpingo-oophorectomy without systematic (radical) lymph nodes dissection at our centers from June, 2002, to November, 2011. Descriptive statistics were explored as medians (interquartile range) or frequencies (percentages), as appropriated, and the Kaplan–Meier method was applied for survival estimation. Results: eighty-three patients who underwent surgical treatment with no lymph node dissection (n = 20; 24.1%) or with only a sampling procedure (n=63; 75.98%) were selected for analysis. Among these patients, 27 (32.53%) underwent surgery alone and 56 (67.46%) received some adjuvant treatment. Postoperative complications occurred in five patients (6.02%). Over a median follow-up of 27.4 months (Q25 = 13.7 – Q75 = 46.5), 15 (18.07%) patients suffered from relapses and 11 deaths occurred as result of disease recurrence. Cumulative 1, 2 and 3-year disease- free survivals were 97.32, 91.18 and 78.02%, respectively. Conclusion: on a case-by-case basis, the surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy did not seem to decrease survival outcomes and presented low rates of surgical morbidity in our experience, but was also related to a high rate use of adjuvant therapy. .

Objetivo: descrever a experiência dos autores com o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical. Métodos: realizou-se estudo de coorte retrospectivo envolvendo um subgrupo de pacientes com câncer de endométrio em estágio clínico precoce tratadas com histerectomia e salpingo-ooforectomia sem linfadenectomia radical, em dois centros pernambucanos, de junho de 2002 a novembro de 2011. As variáveis foram descritas como mediana (intervalo interquartílico) ou frequências (percentuais), utilizando- se o método de Kaplan-Meier para a estimativa das taxas de sobrevivência. Resultados: oitenta e três pacientes submetidas a tratamento cirúrgico sem dissecção linfonodal (n = 20, 24,1%) ou com dissecção apenas por amostragem (n = 63; 75,98%) foram selecionadas para análise. Entre essas pacientes, 27 (32,53%) foram tratadas somente com cirurgia e 56 (67,46%) receberam tratamento adjuvante. Cinco pacientes apresentaram complicações pós-operatórias (6,02%). Durante o acompanhamento mediano de 27,4 meses (Q25 = 13,7 - Q75 = 46,5), 15 (18,07%) pacientes apresentaram recorrência, dentre as quais 11 faleceram em decorrência da recidiva neoplásica. Observou-se sobrevivência cumulativa proporcional livre de doença em um, dois e três anos de 97,32, 91,18 e 78,02%, respectivamente. Conclusão: em um contexto de indicação caso-a-caso, o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical parece não ter prejudicado a sobrevivência e apresentou baixas taxas de morbidade cirúrgica em nossa experiência, mas também foi acompanhado de elevada utilização de terapia adjuvante. .

Preoperative serum albumin as a prognostic factor in patients with upper urinary tract urothelial carcinoma

Purpose The study evaluated whether preoperative measures of the C-reactive protein-based systemic inflammatory response may predict cancer survival independent of tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC). Materials and Methods Between September 1999 and October 2010, 181 patients submitted to radical nephroureterectomy were available for evaluation. Multivariate survival analyses were performed using Cox’s proportional hazards model and the coefficient for each factor was divided by the highest coefficient, multiplied by 4, and rounded to the nearest integer. Results Multivariate analyses showed that tumor location, pathologic T stage, lymphovascular invasion, margin status, and albumin level were independent contributors. The bootstrap-corrected C statistics of the model were 0.813 for disease-specific survival and 0.755 for overall survival, respectively. For time to disease-specific and overall mortality for patients, integrated area under the curve values were 0.792 and 0.739, respectively. When patients were clustered into three groups according to their model-predicted survival, the 5-year disease-specific survival in the low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival (p<0.001). Decision curve analysis revealed that the use of model was associated with net benefit gains relative to the treat-all strategy. Conclusions   Pretreatment albumin is a simple biomarker based on routinely available well-standardized measures, and is not an expensive and time-consuming process. Hypoalbuminemia is an independent marker of poor prognosis in patients with upper urinary tract urothelial carcinoma. .

Comparison of Radical Cystectomy with Conservative Treatment in Geriatric ( 80) Patients with Muscle-Invasive Bladder Cancer

Introduction The aim of this study was to compare overall survival in elderly patients (≥ 80 years) with muscle-invasive bladder cancer (MIBC) undergoing either radical cystectomy (RC) or conservative treatment. Material and Methods We performed a retrospective, comparative analysis of overall- and cancer-specific survival in octagenarians with MIBC (≥ pT2) submitted to RC or conservative treatment. Uni- and multivariable Cox regression analysis were performed to assess predictors of overall survival. Cumulative hospital stay was also analyzed for all patients. Results The RC-group consisted of 33 patients with a mean age of 82.3 years (IQR 80.4-85.4 years) and the bladder preservation a cohort of 35 patients aged 83.8 years (IQR 81.8-88.2 years). No difference was detectable for overall survival (15.9 months versus 9.5 months; p = 0.18) and cancer-specific survival (23.5 months versus 19.5 months p = 0.71) or 90-day mortality (6.1% versus 14.3%; p = 0.43) between the two groups. Patients who received conservative treatment had a shorter cumulative length of hospital stay (p = 0.001). Age at the time of transurethral resection of the bladder (TUR-B) was an independent predictor of the overall survival (p = 0.004). Conclusions In this retrospective study, no clear survival benefit was observed for patients ≥ 80 years submitted either to radical cystectomy or conservative treatment. There was however a trend favoring radical cystectomy but this did not approach statistical significance. Octagenarians that underwent RC however spent more of their remaining lifetime in the hospital than those treated conservatively. .

Invasive bladder cancer in the eighties: transurethral resection or cystectomy?

PURPOSE: Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) or transurethral resection (TUR) in our institution. MATERIALS AND METHODS: We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9 percent). The American Society of Anesthesiology (ASA) score was III or IV in 23 patients (85.1 percent). Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8 percent) patients. RESULTS: Pathological stage of the RC specimen was pT3 in 18 cases (66.7 percent). Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6 percent), with an overall survival (OS) of 42.94 percent, and cancer-specific survival (CSS) of 60.54 percent. In patients submitted to TUR, clinical stage was T2 in 36 cases (50 percent). The mean hospital stay was 7 days, with a readmission rate (RR) of 87.5 percent. OS and CSS was less than 20 percent. CONCLUSIONS: RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.

Survival of a cohort of patients with Intermediate and advanced gall bladder cancer treated with a prospective therapeutic protocol / Sobrevida de uma coorte de pacientes com câncer na vesícula intermédio e avançado tratados com um protocolo terapêutico de natureza prospectiva

PURPOSE: To evaluate the results of a prospective therapeutic protocol with long-term follow up in terms of survival rates in a cohort of patients treated with Intermediate and Advanced GBC (GBC). METHODS: Prospective cohort of patients with intermediate and advanced stages of GBC treated between 1996 and 2006. All cases were treated with a partial hepatic segmentectomy on segments IVb and V and a regional lymph node dissection and six cycles of out-patient chemotherapy (5-FU and leukovorin). With an average follow-up of 31.5 months, the morbidity, operative mortality, hepatic and lymphatic infiltration and actuarial survival were measured. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact test and non-parametrical tests and Kaplan Meier survival curves. Also logistic regression and proportional risk of Cox were applied. RESULTS: 40 patients were included in this protocol, with an average age of 59.5 years (40-85 years), of which 28 were women (70 percent). Depth of wall infiltration: muscular 8 patients (20 percent), subserosal 12 patients (30 percent), serosal 12 patients (30 percent) and perivesicular adipose tissue 8 patients (20 percent). The series morbidity was 27.5 percent. There was no operative mortality. The chemotherapy was well tolerated. The overall actuarial survival in the series was 50 percent at 60 months. CONCLUSION: Our protocol treatment has morbidity, mortality and survival rates similar to previously reported series.

OBJETIVO: Avaliar os resultados de resultados da aplicação de um protocolo terapêutico de natureza prospectiva, com seguimento em longo prazo nos termos de taxas de sobrevivência em uma coorte de pacientes operados com carcinoma vesícula biliar (CVB) intermédio e avançado. MÉTODOS: A coorte prospectiva de pacientes com estágios intermediários e avançados de CVB tratados entre 1996 e 2006. Todos os casos foram tratados com uma segmentectomia hepática parcial em segmentos IVb e V e uma dissecção linfonodal regional e seis ciclos de quimioterapia de ambulatório (5-FU e leukovorin). Com um tempo de seguimento médio de 31,5 meses, a morbidade, mortalidade operatória, hepático e infiltração linfática e atuarial de sobrevida foram medidas. Estatísticas descritivas foram aplicadas, bem como análise bivariada aplicando o teste exato de Fisher, testes não-paramétricos, curvas de sobrevida Kaplan Meier e técnica de regressão logística e risco proporcional de Cox. RESULTADOS: Foram incluídos 40 pacientes neste protocolo, com uma média de idade de 59,5 anos (40-85 anos), dos quais 28 eram mulheres (70 por cento). Profundidade de infiltração parede: muscular 8 pacientes (20 por cento), subserosal 12 pacientes (30 por cento), serosas 12 pacientes (30 por cento) e perivesicular no tecido adiposo, 8 pacientes (20 por cento). A série morbidade foi de 27,5 por cento. Não houve mortalidade operatória. A quimioterapia foi bem tolerada. A sobrevida global atuarial da série foi de 50 por cento em 60 meses. CONCLUSÃO: Nosso protocolo tem tratamento morbidade, mortalidade e taxas de sobrevivência semelhantes às relatadas anteriormente série.

Avaliação dos fatores clínicos e do tratamento em pacientes com carcinoma indiferenciado da nasofaringe / Assessment of clinical and therapeutic factors in patients with nasopharyngeal undifferentiated carcinoma

O carcinoma de nasofaringe é neoplasia rara, com incidência maior em países do Sudeste Asiático. OBJETIVO: Avaliar dados demográficos, clínicos, terapêuticos e prognósticos do carcinoma indiferenciado de nasofaringe em um serviço de referência. CASUÍSTICA E MÉTODO: Estudo retrospectivo de 46 pacientes, de janeiro de 1978 a agosto de 2000. Nenhum paciente foi previamente tratado e não apresentava tumor sincrônico e metástase à distância. RESULTADOS: A idade variou de 14 a 78 anos (média, 46), sendo 35 (76 por cento) pacientes masculinos. Todos eram de etnia caucasiana ou afro-brasileira. O tempo de história variou de 1 a 48 meses (média, 7), sendo 47 por cento tabagistas e 33 por cento etilistas. O sintoma mais relatado foi a presença de nódulo no pescoço (34 pacientes). Quanto ao estadiamento clínico, 22 foram estadiados como T1/T2 e 24 como T3/T4, enquanto 24 foram classificados como N2 e 16, N3. O tratamento instituído com finalidade curativa foi a radioterapia, associada à quimioterapia concomitante nos estádios III e IV. Dos 27 pacientes com seguimento após o tratamento inicial, 52 por cento apresentavam-se vivos e livres de doença há três anos. CONCLUSÃO: Os pacientes eram de estádio clínico avançado, com sobrevida livre de doença em três anos de 52 por cento.

The nasopharyngeal carcinoma (NPC) is a rare cancer with a high incidence in Southern Asia. AIM: to study the demographic, clinical, therapeutic, and prognostic factors of nasopharyngeal undifferentiated carcinoma in a reference service. MATERIALS AND METHODS: A retrospective study was made of 46 patients from January 1998 to August 2000. The patients had no previous treatment and did not present any evidence of synchronous tumors or distance metastases. RESULTS: The age ranged from 14 to 78 years (mean = 46 years); 35 (76 percent) patients were male. All patients were Caucasian or African-Brazilian. The onset of initial symptoms ranged from 1 to 48 months (mean = 7 months); 47 percent of the subjects smoked tobacco and 33 percent consumed alcoholic beverages. A lump in the neck was the most frequent symptom (34 patients). Twenty-two patients were clinically staged as T1/T2 and 24 patients as T3/T4; 24 patients were classified as N2, and 16 patients were staged as N3. Curative treatment consisted of radiotherapy and simultaneous chemotherapy in clinical stages III and IV. Of 27 patients that were monitored, 52 percent were alive with no evidence of disease after three years. CONCLUSION: All patients were in advanced clinical stages of the disease. The three-year disease-free survival rate was 52 percent.

Cáncer de vesícula biliar: Tendencia y distribución del riesgo en Chile / Gallbladder cancer: trend and risk distribution in Chile

Background: Gallbladder cancer (GBC) is the first cause of death by cancer among Chilean women and mortality has not improved in the last 20 years. Aim: To study GBC mortality trend from 1985-2002, analyze risk differentials by age, sex, geographic region and accessibility to surgery. Material and Methods: Mortality data was obtained from death certificate databases. Population data was obtained from the census and biliary surgery information, from Ministry of Health registries. Standardized Mortality rates were based in the world population; trend was analyzed with point of change methods. Results: From 1985 to 2002, 27,183 GBC deaths occurred, 1,510 per year. The absolute number of deaths increased in 65% but standardized mortality rates remained unchanged at 11.3 per 100,000. These were higher among women than men (15.6 and 7.0, respectively, with a risk ratio of 2.2). Sex ratio peaked at ages 35-54 with risk ratio of 4.1. Death risk increased from North to South, peaking in poorer areas, especially in places with rural population and Mapuche ethnic admixture. Mortality appear to correlate with the rate of people waiting for gallbladder surgery, but not reaching statistical significance (r2 0.27, ns). Compared with other countries, Chile has a higher rate of GBC deaths in relation to its gross domestic product per capita. Conclusions: There is a high and persistent persistent risk for GBC in Chile, particularly among women, from the Southern regions where gallbladder surgery is insufficient for the needs, as reflected by the rates of people waiting for biliary surgery. GBC rates could be dropped by offering gallbladder surgery to everyone waiting for it and to those incident cases with gallstones.