Current approaches to immunotherapy in noncolorectal gastrointestinal malignancies

Noncolorectal gastrointestinal (GI) malignancies are among the most frequently diagnosed cancers. Despite the undeniable progress in systemic treatments in recent decades, further improvements using cytotoxic chemotherapy seem unlikely. In this setting, recent discoveries regarding the mechanism underlying immune evasion have prompted the study of molecules capable of inducing strong antitumor responses. Thus, according to early data, immunotherapy is a very promising tool for the treatment of patients with GI malignancies. Noncolorectal GI cancers are a major public health problem worldwide. Traditional treatment options, such as chemotherapy, surgery, radiation therapy, monoclonal antibodies and antiangiogenic agents, have been the backbone of treatment for various stages of GI cancers, but overall mortality remains a major problem. Thus, there is a substantial unmet need for new drugs and therapies to further improve the outcomes of treatment for noncolorectal GI malignancies. "Next-generation" immunotherapy is emerging as an effective and promising treatment option in several types of cancers. Therefore, encouraged by this recent success, many clinical trials evaluating the efficacy of immune checkpoint inhibitors and other strategies in treating noncolorectal GI malignancies are ongoing. This review will summarize the current clinical progress of modern immunotherapy in the field of noncolorectal GI tumors.

Carcinoid syndrome: update on the pathophysiology and treatment

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance status is scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.

A "miracle" cancer drug in the era of social media: A survey of Brazilian oncologists' opinions and experience with phosphoethanolamine / Uma "milagrosa" droga contra o câncer na era da mídia social: uma pesquisa sobre a opinião e a experiência dos oncologistas brasileiros com a fosfoetanolamina

Summary Introduction: Patients who are treating cancer have often used alternative therapies. In the internet era, information can be broadcasted widely, and this happened with phosphoethanolamine in Brazil, where this substance was claimed by the population to be the "cure for cancer." Method: This is a cross-sectional study developed by the Brazilian Society of Clinical Oncology (SBOC). An objectively structured questionnaire was sent by e-mail and SMS to active MDs members of the SBOC. Descriptive statistics was used to evaluate the data. Statistical significance between the variables was tested by Pearson's Chi-squared test (p<0.05 was considered significance). Results: The survey was sent to 1,072 oncologists, and 398 (37.1%) answered at least part of it. One hundred and fifteen (28.9%) had followed patients who had used phosphoethanolamine. Among these, 14 (12.2%) observed adverse events and four (3.5%) attributed clinical benefit to the substance. Most of the oncologists (n=331; 83.2%) believe that it should only be used as part of a clinical trial protocol. Most physicians did not recommend this drug to their patients (n=311; 78.1%). Oncologists in Southeast, South and Midwest Brazil were more likely to have patients taking the drug compared to the Northern and Northeastern regions. Conclusion: This is the first survey to assess the opinion and experience of oncologists about this alternative therapy. Most oncologists in Brazil do not believe that synthetic phosphoethanolamine is active in cancer treatment, do not recommend its use without proper evaluation, and state that it should only be available to patients in the context of clinical trials.

Resumo Introdução: Alguns pacientes com diagnóstico de câncer utilizam terapias alternativas. Na era da internet, as informações podem se dissipar de forma rápida e abrangente, como foi o caso da fosfoetanolamina no Brasil, onde foi aclamada pela população como sendo a "cura para o câncer". Método: Trata-se de um estudo transversal desenvolvido pela Sociedade Brasileira de Oncologia Clínica (SBOC). Através de e-mail e SMS, enviou-se um questionário com perguntas objetivas para oncologistas membros ativos da SBOC. Os dados foram avaliados por meio de estatística descritiva. A significância estatística entre as variáveis ​​foi testada pelo teste Qui-quadrado de Pearson (p<0,05 foi considerado significativo). Resultados: O questionário foi enviado para 1.072 oncologistas, tendo 398 (37,1%) respondido pelo menos parte dele. Cento e quinze (28,9%) tinham pacientes que fizeram uso da fosfoetanolamina. Desses, 14 (12,2%) observaram eventos adversos e quatro (3,5%) atribuíram benefício clínico para a substância. A maioria (n=331; 83,2%) acreditava que ela só deveria ser utilizada dentro de um ensaio clínico. A principal recomendação dada aos pacientes foi contra o seu uso (n=311; 78,1%). Oncologistas das regiões Sudeste, Sul e Centro-Oeste tiveram mais pacientes que tomaram a substância quando comparados com as regiões Norte e Nordeste. Conclusão: Este é o primeiro estudo que avalia a opinião dos oncologistas sobre essa terapia alternativa e sua experiência. A maioria dos oncologistas brasileiros não acredita que a fosfoetanolamina sintética seja ativa no tratamento do câncer, não recomendando seu uso sem avaliação adequada, e afirmam que a substância só deve estar disponível no contexto de ensaios clínicos.

Adherence to colonoscopy recommendations for first-degree relatives of young patients diagnosed with colorectal cancer

OBJECTIVES:Colorectal cancer is the third leading cause of cancer death in the United States. The American College of Gastroenterology recommends screening for first-degree relatives of patients diagnosed with colorectal cancer before the age of 50. A colonoscopy is one of the most commonly recommended exams due to its specificity and the possibility to resect pre-malignant lesions. Nevertheless, the rate of physician adherence to this recommendation is unknown.METHODS:This transversal study was performed at a major cancer center in Brazil with 62 patients, aged 18 to 50, who completed a questionnaire on information received from their physicians regarding screening their first-degree relatives. We used the answers from patients who provided explicit consent.RESULTS:Two hundred and three patients were eligible to participate and 93 (45.8%) agreed to complete the questionnaire. Twenty-three questionnaires (24.73%) were returned and 39 were completed by telephone. Of the patients who answered the questionnaire, 39 (62.9%) had received a colonoscopy recommendation for their first-degree relatives and 23 (37.1%) were not informed of the recommendation. Among the patients who received the recommendations, 20.51% affirmed that all relatives completed the exam and 51.28% stated that no relatives completed the exam.DISCUSSION:The adherence rate of our physicians to the ACG guideline recommendations was 62.9%. Considering that our study was performed at a leading center for cancer treatment in Latin America, we had expected better adherence. The results show that adherence to the colorectal cancer screening recommendations for high-risk patients must be improved.