Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience

ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Consensus on diagnosis and management of non-metastatic castration resistant prostate cancer in Brazil: focus on patient, selection, treatment efficacy, side effects and physician's perception according to patient comorbidities

ABSTRACT Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. Objective: To present survey results on management of M0 CRPC in Brazil. Design, setting, and participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.

Second brazilian consensus on the treatment of advanced prostate cancer: a SBOC-SBU-SBRT panel review

ABSTRACT Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The first Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Impact of 68GA-PSMA PET / CT on treatment of patients with recurrent / metastatic high risk prostate cancer - a multicenter study

ABSTRACT Purpose: The purpose of our study was to evaluate the clinical impact of 68Ga-PSMA PET / CT in the setting of biochemical recurrence of prostate cancer. Materials and Methods: We retrospectively evaluated 125 prostate cancer patients submitted to the 68Ga-PSMA PET / CT due to biochemical recurrence. The parameters age, Gleason score, PSA levels, and the highest SUVmax were correlated to potential treatment changes. The highest SUVmax values were correlated with age and Gleason score. The median follow-up time was 24 months. Results: 68Ga-PSMA PET / CT led to a treatment change in 66 / 104 (63.4%) patients (twenty-one patients were lost to follow-up). There was a significant change of treatment plan in patients with a higher Gleason score (P = 0.0233), higher SUVmax (p = 0.0306) and higher PSA levels (P < 0.0001; median PSA = 2.55 ng / mL). Conclusion: 68Ga-PSMA PET / CT in prostate cancer patients with biochemical recurrence has a high impact in patient management.

First brazilian consensus of advanced prostate cancer: recommendations for clinical practice

ABSTRACT Introduction Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. Objectives This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Materials and Methods Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. Results and Conclusions The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Castration-resistant prostate cancer: systemic therapy in 2012

Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

Tumor estromal gastrointestinal: análise de 146 casos do centro de referência do Instituto Nacional do Câncer - INCA / Gastrointestinal stromal tumor: analysis of 146 cases of the center of reference of the National Cancer Institute - INCA

OBJETIVO: Avaliar os resultados do tratamento de GIST no INCA. MÉTODOS: Análise retrospectiva de todos os casos de GIST tratados no INCA no período de 1997 a 2009. RESULTADOS: Analisamos 146 pacientes, com média de idade de 44,5 anos e predomínio do sexo feminino. O principal sintoma foi dor abdominal. Tivemos ocorrência de segundo primário em 22 por cento dos casos e na imuno-histoquímica, 92 por cento foram positivos para CD117. A localização mais frequente foi estômago e predominou o grupo de alto risco. A cirurgia foi R0 (extenso) em 70 por cento e os principais sítios de metástases foram fígado e peritônio. A sobrevida global foi, respectivamente, em dois e cinco anos de 86 por cento e 59 por cento. Houve significante diferença entre a sobrevida global (p=0,29) do grupo de alto risco versus os demais. CONCLUSÃO: Os nossos pacientes apresentam-se principalmente sob forma de doença de alto risco com repercussão óbvia na sobrevida. O uso de Imatinib melhorou a sobrevida dos pacientes com doença metastática e recidivada. Devemos estudar seu uso no cenário de adjuvância e neoadjuvancia visando melhorar os índices do grupo de alto risco. A criação de centros referenciais é uma necessidade para o estudo de doenças pouco frequentes.

OBJECTIVE: To evaluate the treatment of GIST in INCA. METHODS: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009. RESULTS: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22 percent of cases and 92 percent of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70 percent of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86 percent and 59 percent. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other. CONCLUSION: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

Estudo de fase I/II de erlotinib (OZI-774) combinado com radioterapia e cisplatina em pacientes com carcinoma epidermóide de cabeça e pescoço, localmente avançado / Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Propósito: Erlotinib, um inibidor oral da Tirosina Quinase posicionada junto ao domínio intracelular do EGFR, é uma droga ativa contra Carcinoma de Células Escamosas de Cabeça e Pescoço (CECCP) avançado e possivelmente possui sinergismo com a quimioterapia e radioterapia. O objetivo deste trabalho foi avaliar a dose adequada, a segurança e eficácia do Erlotinib associado à combinação padrão de quimioterapia e radioterapia no CECCP localmente avançado. Pacientes e Métodos: Pacientes com CECCP localmente avançado são o fundamento deste ensaio clínico de FaseI/II, cujo tratamento consistiu da combinação de Cisplatina 100mg/m² intra-venoso (iv), administrada nos dias 8, 29 e 50 do tratamento; e radioterapia na dose de 70.2Gy administrada em 39 frações a partir do Dia 8. Durante a fase I do estudo a dose de Erlotinib foi escalonada (50 mg, 100mg e 150mg por via oral, tomado uma vez ao dia) em consecutivas coortes de três pacientes. Toxicidade dose limitante (TDL) foi avaliada pelos critérios do CTCAE e do RTOG e foi definida como qualquer evento grau 4 que requeresse interrupção da radioterapia. A fase II do estudo foi iniciada 8 semanas após o último registro de paciente na fase I. Resultados: Nove pacientes foram recrutados na fase I e 28 na fase II; todos foram avaliados para análise de segurança e eficácia. Nenhuma TDL ocorreu durante o escalonamento na fase I e foi recomendada para fase II a dose de 150mg ao dia de erlotinib. As toxicidades não hematológicas observadas mais frequentes foram náusea e vômitos, disfagia, estomatite, xerostomia, dermatite no campo de radiação, rash acneiforme, e diarréia. Dos 31 pacientes que usaram Erlotinib na dose de 150mg/dia, 23 (74%, 95% CI 56,8% - 86,3%) obtiveram resposta completa, 3 apresentaram doença residual que foi resgatada imediatamente com cirurgia e ficaram sem evidência de doença, 4 permaneceram com doença residual inoperável, e 1 morreu de sepse durante o tratamento. Com seguimento médio de 37 meses...

Purpose: Erlotinib, an oral tyrosine-kinase inhibitor, is active against squamous cell carcinoma of the head and neck (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Patients and Methods: Phase I/II trial of cisplatin 100 mg/m2 on days 8, 29 and 50; and radiotherapy 70 Gy starting on day 8. During the phase I, erlotinib dose was escalated (50 mg, 100 mg and 150 mg) in consecutive cohorts of three patients, starting on day 1 and continued during radiotherapy. Dose-limiting toxicity (DLT) was defined as any grade 4 event requiring radiotherapy interruptions. Phase II initiated 8 weeks after the last phase I enrollment. Results: Nine patients were accrued in the phase I and 28 in the phase II; all were evaluable for efficacy and safety. No DLT occurred in the phase I and the recommended phase II dose was 150mg. The most frequent non-hematological toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients in the erlotinib 150 mg daily dose, 23 (74%, 95% CI 56.8% 86.3%) had a complete response, 3 were disease-free after salvage surgery, 4 had an inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months follow-up, the 3-year progression-free and overall survival were 61 and 72% respectively. Conclusion: This combination appears safe, has encouraging activity and deserves further studies in locally advanced HNSCC.

Estudo de fase I/II de Erlotinib (OZI-774) combinado com a radioterapia e cisplatina em pacientes com carcinoma epidermóide de cabeça e pescoço, localmente avançado / Phase I/II study of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Propósito: Erlotinib, um inibidor oral da tirosina quinase posicionada junto ao domínio intracelular do EGFR, é uma droga ativa contra carcinoma de células escamosas de cabeça e pescoço (CECCP) avançado e possivelmente possui sinergismo com a quimioterapia e radiotetapia. O objetivo deste trabalho foi avaliar a dose adequada, a segurança e eficácia do Erlotinib associado à combinação padrão de quimioterapia e radioterapia no CECCP localmente avançado. Pacientes e métodos: Pacientes com CECCP localmente avançado são o fundamento deste ensaio clínico de Fase I/II, cujo tratamento consistiu da combinação de Cisplatina 100mg/m2 intra-venoso (iv), administrada nos dias 8, 29 e 50 do tratamento; e radioterapia na dose de 70.2gy administrada em 39 frações a partir do dia 8. Durante a fase I do estudo a dose de erlotinib foi escalonada (50mg, 100mg e 150mg por via oral, tomando uma vez ao dia) em consecutiva coortes de três pacientes. Toxidade dose limitante (TDL) foi avaliada pelos critérios do CTCAE e do RTOG e foi definida como qualquer evento grau 4 que requeresse interrupção da radioterapia. A fase II do estudo foi iniciada 8 semanas após o último registro de paciente na fase I. Resultados:

Phase II trial of neoadjuvant gemcitabine and cisplatin in patients with resectable bladder carcinoma

OBJECTIVES: Gemcitabine and cisplatin (GC) is an active combination in the treatment of metastatic bladder cancer. We have prospectively analyzed the efficacy and tolerability of GC as neoadjuvant treatment of invasive bladder cancer MATERIALS AND METHODS: In this single-institution phase II trial, patients with muscle-invasive transitional cell carcinoma received three cycles of gemcitabine 1200 mg/m² on days 1 and 8 with cisplatin 75 mg/m² on day 1 prior to surgery. Radiologic response was evaluated by computed tomography and magnetic resonance imaging. All patients were referred to surgery after chemotherapy completion RESULTS: Between June 2002 and March 2005, 22 patients (19 males) were enrolled. Median age was 63 years. Initial stage was II (T2) in 11 and III (T3-4) in 11 patients. Median follow-up is 26 months (4-43). Partial or complete radiologic response rate was documented in 13 out of 20 assessable patients (70 percent). One patient was excluded due to sarcomatoid carcinoma at definitive pathologic examination. Cystectomy was performed in 15 patients and pelvic radiotherapy in four patients. Nine out of 21 patients (43 percent) relapsed and four (19 percent) died due to disease progression. Complete pathologic response was observed in four patients (26.7 percent of 15). Median progression-free survival was 27 months (CI 95 percent not reached) with median overall survival of 36 months (CI 95 percent: 28.7 - 43.3). Grade III/IV toxicity was infrequent, with no deaths due to chemotherapy CONCLUSIONS: The combination of GC is effective and well-tolerated when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact on the overall survival of these patients.

Análise de fatores clínicos, histopatológico e moleculares (p53, Ki67, Bcl2 e PCNA) preditivos de resposta terapêutica à quimioterapia e radioterapia em pacientes com carcinoma espinocelular de laringe e orofaringe / Analysis of clinical, histopathological and molecular (P53, Ki-67, Bcl-2 and PCNA) factors predictive of the therapeutic response to chemotherapy and radiotherapy in patients with laryngeal and oropharyngeal squamous cell carcinoma

Introdução: tratamento padrão-ouro para pacientes com carcinoma espinocelular (CEC) em estádios clínicos (EC) III e IV é o cirúrgico, seguido de radioterapia (RXT). Na preservação de órgãos, vários esquemas com radioterapia e quimioterapia são estudados. No entanto, quais pacientes irão melhor responder a esses protocolos é um questionamento ainda sem resposta. Objetivos: avaliar 21 fatores clínicos e um histopatológico, assim como a expressão p53, Bcl2, Ki67 e PCNA como fatores preditivos de resposta a radioterapia e quimioterapia em pacientes com CEC de laringe e orofaringe. Pacientes e Método: no período de janeiro de 2000 a agosto de 2003, 57 pacientes com CEC da laringe e orofaringe (EC III e IV) foram tratados com RXT e quimioterapia no INCA-MS-RJ. Avaliamos, através de análise imunoistoquímica nos blocos de parafina desses pacientes, a expressão da p53, Bcl2, Ki67 e PCNA na mucosa normal, assim como no tumor. Essa expressão foi correlacionada com a resposta ao tratamento, assim como avaliamos a associação de 22 fatores com essa resposta. Resultados: a toxicidade do tratamento foi alta, levando a 100% dos pacientes a interromperem o tratamento de alguma forma. Resposta completa foi observada em 68,4% dos casos, com sobrevida global de 58,24% e sobrevida livre de doença de 56,4%. Dos 22 fatores preditivos, apenas a ausência de hiperalimentação por sonda nasoenteral (SNE) (p=0,0006), tamanho do tumor (T) (p=0,009) e ausência de traqueostomia prévia (p=0,0002) foram preditivos de boa resposta ao tratamento (análise univariada). A expressão negativa do Bcl2 no tumor, na mucosa e em ambos (p=0,017, 0,04 e 0,028, respectivamente) foram preditivos de boa resposta (análise univariada), com probabilidade, respectivamente, de 3,64; 5,29 e 7,68 vezes maior de resposta quando comparado com a população que o expressou. A expressão positiva do Bcl2 foi de 25,5%, do p53 de 55,3%, do Ki67 de 82,6%, do PCNA de 76%. Nenhuma dessas expressões teve impacto na resposta ao tratamento. Entretanto, ao realizarmos a análise multivariada, apenas a ausência da traqueostomia prévia ao tratamento (p=0,0056) e ausência de hiperalimentação por SNE (p=0,002) foram fatores preditores de boa resposta. Conclusões: das 22 variáveis, apenas a ausência de hiperalimentação pela SNE e ausência de traqueostomia prévia foram fatores preditivos de boa resposta ao tratamento. De uma forma isolada (análise univariada), a não expressão imunoistoquímica do Bcl2 no tumor, na mucosa e em ambos (principalmente) estiveram associados a uma melhor resposta terapêutica.

Introduction: the standard treatment for patients with HNSCC stages III and IV is surgical plus radiation therapy (RT). In order to preserve the organs, several schemes using RT and chemotherapy (CT) have been studied. Nevertheless, the patients submitted to this treatment who will better respond to these protocols is not known yet. Objective: to evaluate 22 factors as well as the expressions of proteins p53, Bcl2, Ki67 and PCNA as predictive factors, in response to RT and CT in patients with laryngeal and oropharyngeal SCC. Materials and methods: from January, 2000 to August, 2003, 57 patients with laryngeal and oropharyngeal SCC (Stages III and IV) were treated with RT and CT at INCA-MS-RJ. We analyzed the paraffin blocks of those patients throughout immunohistochemistry study. The positive and negative expressions of p53, Bcl2, Ki67 and PCNA on normal mucosa,as well as in the tumor (and in both of them). The expression was correlated to the response of treatment, as we analyzed the association of 22 clinical factors of patients showing this response. Results: the toxicity of treatment was high, taking 100% of patients to somehow interrupt the treatment. A complete response was observed in 68.4% of the cases, with overall survival rate of 58.24% and disease-free survival rate of 56.4%. Among the 22 predictive factors, only the lack of hypernutrition through nasoenteral tube (p=0.0006), tumor size (T), p=0.009 and the lack of tracheotomy were predictive of a better response to the treatment (univariated analysis). Only the Bcl2 negative expression in the tumor, mucosa and in both (p=0.017, 0.04 and 0.028, respectively) were predictive of a better response (univariated analysis) with support of 3.64; 5.29 and 7.68, respectively, much higher when compared to the population who expressed it. Positive expression of Bcl2 was 25.5%; p53 55.3%; Ki67 82.6%; PCNA 76%. None of those expressions caused any impact to response of treatment. Nevertheless, when a multivariated analysis was made, only the lack of previous tracheotomy to treatment (p=0.0056) and the lack of hypernutrition through NET (p=0.002) were predictive factors for a better result. Conclusions: among 22 predictive factors, only the lack of hypernutrition through SNE and the lack of previous tracheotomy were predictive factors for better results. Throughout an univariated analysis the non-immunohistochemistry expression of Bcl2 in the tumor, on mucosa and in both (mainly), had a good impact in therapeutic response.

Advances in radiochemotherapy in the treatment of head and neck cancer

Novos avanços vêm sendo incorporados no tratamento radio e quimioterápico do Câncer Epidermóide de Cabeça e Pescoço. Apesar do prognóstico reservado dos tumores avançados, não devemos esquecer da possibilidade de incorporarmos protocolos combinados de quimioterapia e radioterapia com intuito de preservação de órgãos ou paliação em estágios de doença recorrente ou localmente avançada que não são bons candidatos à cirurgia. Nesse contexto, há uma necessidade urgente de incorporar questionários de qualidade de vida e avaliação funcional nos estudos de preservação de órgãos, além de assegurar a importância do resgate cirúrgico depois de protocolos radio-quimioterápicos. Os autores realizam uma extensa revisão dos avanços que vêm ocorrendo no tratamento não cirúrgico do câncer de cabeça e pescoço, com especial atenção à diferentes protocolos de radioterapia, novas combinações de quimioterapia, terapia e marcadores moleculares bem como a incorporação de terapia de re-irradiação e tratamento adjuvante após cirurgia.

Quimioterapia neoadjuvante em câncer de mama localmente avançado: análise imunohistoquímica é preditiva da resposta à quimioterapia / Neoadjuvant chemotherapy for locally advanced breast cancer: imunohistochemical analysis is predictive of response to chemotherapy

A quimioterapia é o tratamento padrão inicial para câncer de mama localmente avançado. A correlação entre a resposta à quimioterapia neoadjuvante e fatores prognósticos pode ser útil nesta doença. De setembro de 1996 a dezembro de 1997, 25 pacientes portadoras de câncer de mama localmente avançado (UICC - estádio IIIA, IIIB e inflamatório (1), foram submetidas a 4 ciclos de quimioterapia neoadjuvante com doxorrubucina 60mg/m² e ciclofosfamida 600mg/m² a cada 21 dias, mastectomia à Patey e tratamento adjuvante. A resposta clínica e patológica foi correlacionada com marcadores obtidos através de análise imunohistoquímica da biópsia do tumor. Os marcadores analisados foram: receptores hormonais, p53, HER/neu (cerb-B2), MIB, grau nuclear, PCNA. A resposta clínica objetiva foi de 74 porcento. Vinte e um de 23 pacientes (91 porcento) analisadas foram submetidas à cirurgia. Quatro pacientes não apresentavam doença microscópica na mama (19 porcento). Destas pacientes, 2 também não apresentavam doença em linfonodos axilares, enquanto 4 apresentavam doença residual na mama de até 2 cm (19 porcento). Todos os marcadores apresentaram positividade em percentuais elevados...

Quimioterapia neo-adjuvante e câncer de mama localmente avançado: a análise imuno-histoquímica é preditiva da resposta à quimioterapia / Neoadjuvant chemotherapy for locally advanced breast cancer imunohistochemical analysis is predictive of response to chemotherapy

A quimioterapia é o tratamento-padräo inicial para câncer de mama localmente avançado. A correlaçäo entre a resposta à quimioterapia neo-adjuvante e fatores prognósticos pode ser útil na abordagem desta doença. De setembro de 1996 a dezembro de 1997, 25 pacientes portadoras de câncer de mama localmente avançado (estágios IIIA, IIIB e inflamatório) foram submetidas a quatro ciclos de quimioterapia neo-adjuvante com doxorrubicina 60mg/m2 e ciclofosfamida 600mg/m2 a cada 21 dias, mastectomia à Patey e ao tratamento adjuvante. A resposta clínica e a patológica foram correlacionadas com marcadores obtidos por meio de análise imuno-histoquímica da biópsia do tumor. Os marcadores analisados foram:receptores hormonais, p53, HER/neu (cert-B2), MIB-!, grau nuclear e PCNA. A resposta clínica objetiva foi de 74 por cento. Vinte e uma de 23 pacientes (91 por cento) analisados foram submetidas à cirurgia. Quatro pacientes näo apresentavam doença linfonodal, enquanto quatro apresentavam doença residual na mama de até 2 cm (19 por cento). Todos os marcadores apresentaram positividade em percentuais elevados. A positividade do p53 e do MIB apresentou correlaçäo com a resposta ao tratamento quimioterápico neo-adjuvante, porém näo alcançou significância estatística. Os resultados iniciais sugerem uma relaçäo entre a positividade do p53 com a resposta clínica e com a resposta patológica, relaçäo essa que näo é demonstrada em estudos anteriores. Apresença do MIB positivo também esteve associada com uma resposta patológica favorável