PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site.

BACKGROUND: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. METHODS: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. RESULTS: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). CONCLUSION: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Discrepancies in breast cancer's oncological outcomes between public and private institutions in the southeast region of Brazil: a retrospective cohort study.

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers. Patient and methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital-BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group). Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service. Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM.

To Treat or Not to Treat? Dilemmas when Deciding on Antineoplastic Treatment in Patients With Far Advanced Cancers.

Patients with advanced cancers and their oncologists are often faced with difficult treatment decisions, especially when there are borderline situations of expected benefit or increased risk of complications. In this narrative review, we will explore the decision-making process for patients with advanced cancers and provide insights on how to approach this complex task, while didactically dividing the oncologist's assessments according to a mnemonic rule of the ABCDE of therapeutic decision-making. Part A (advanced cancer) recalls that the rule is to be used specifically for advanced cancers. Parts B (potential benefits) and C (clinical conditions and risks) represents the traditional risk vs benefit scale. In Part D, we discuss ways to identify and understand patients' desires, values, preferences, and beliefs. The prognostic estimation, from Part E, may function as an "adjust" for the antineoplastic treatment decision-making. Treatment decisions need to be conducted by skilled oncologists, in a patient-centered care, aiming to promote valuable oncology with lower rates of aggressive care.

Multicenter Database of Patients with Germ-Cell Tumors: A Latin American Cooperative Oncology Group Registry (LACOG 0515).

INTRODUCTION: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers. MATERIALS AND METHODS: This is a retrospective cohort study evaluating male patients diagnosed with GCTs from 2000 to 2018 in 13 Brazilian hospitals. We described baseline characteristics, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 1232 patients were included, with a median age of 30 years. Histology was seminoma in 47.1% and non-seminoma GCT (NSGCT) in 52.9%. The primary tumor site was testis in 96.5%. At diagnosis, clinical stage I was present in 68.1% and 34.7% and clinical stages IS/II/III in 31.9% and 65.2% of patients with seminoma and NSCGT, respectively. Following orchiectomy, 55.2% of patients with clinical stage I were managed with surveillance. The 5-year disease-free survival rates among patients with stage I were 98.0% in seminoma and 92.3% in NSGCT, with 5-year OS of 99.6% and 97.6%, respectively. Among patients with advanced disease (IS, II, and III), the 5-year PFS were 88.7% in seminoma and 68.7% in NSGCT, with 5y-OS of 97.6% and 82.8%, respectively. CONCLUSION: This is the largest Brazilian cohort of GCTs. Our results show a high rate of adjuvant chemotherapy in patients with clinical stage I. Although our data demonstrate slightly inferior PFS compared with the International Germ Cell Cancer Collaborative Group and other contemporary series, the OS rates were similar.

Inflammation and Performance Status: The Cornerstones of Prognosis in Advanced Cancer.

CONTEXT: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. OBJECTIVES: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. METHODS: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan-Meier and Cox regression methods. RESULTS: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI <20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597-11.992) and mGPS (HR 1.843-2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678-8.938) and mGPS (HR 2.103-2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0-1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI >28 kg/m2) to 44% (mGPS 2, BMI <20 kg/m2). CONCLUSION: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts.

Comprehension and Decision-Making Capacity Questionnaire About Palliative Care and Advance Care Planning: A Delphi Study.

Objective(s): To develop a questionnaire that assesses the level of comprehension and decision-making capacity of patients with breast cancer about palliative care and advance care planning. Methods: Questionnaire items were based on the scientific literature. Delphi Consensus, a three-round survey with experts (n = 14), evaluated the relevance, clarity, and redundancies of the items. A pretest with breast cancer patients (n = 15) evaluated whether they comprehended each item and identified doubts or discomforts. Results: The initial questionnaire was composed of 38 items. After the Delphi, 18 items were restructured, six were added, and 16 were removed. In the pretest phase, all items with the survey header, guidelines, and Likert model were evaluated. All items accomplished ≥80% cut-off score and were kept as in the original version. The final version of the questionnaire have 28 itens and five domains: determination, responsibility, independence, self-knowledge, and knowledge of reality. Conclusions: This study represents the first step in the development of a questionnaire that may be used in oncology clinical practice. The main findings revealed that Delphi and pretesting increased the quality of the questionnaire, making it compelling to assess breast cancer patients' comprehension and decision-making capacity about PC and ACP.

Anticancer Treatment Goals and Prognostic Misperceptions among Advanced Cancer Outpatients.

(1) Background: In the context of cancer incurability, the communication processes involving clinicians and patients with cancer are frequently complex. (2) Methods: A cross-sectional study that investigated outpatients with advanced cancers and their oncologists. Both were interviewed immediately after a medical appointment in which there was disease progression and/or clinical deterioration, and were asked about the patient's chance of curability and the goals of the prescribed cancer treatment. The patients were asked whether they would like to receive information about prognosis and how they would like to receive it. The analyses of agreement on perceptions were performed using the Kappa's test. (3) Results: the sample consisted of 90 patients and 28 oncologists. Seventy-eight (87.6%) patients answered that they wanted their oncologist to inform them about their prognosis; only 35.2% (n = 31) of them said they received such information at their present appointment. Regarding how they would prefer prognostic disclosure, 61.8% (n = 55) mentioned that the oncologist should consider ways to keep the patient's hope up; 73% (n = 65) of the patients reported odds >50% of cure. The agreement between oncologists' and their patients' perceptions regarding the treatment goals and curability was slight (k = 0.024 and k = 0.017, respectively). (4) Conclusions: The perceptions of patients and their oncologists regarding the goals of treatment and their chances of cure were in disagreement. New approaches are needed to improve the communication process between oncologists and patients with advanced cancer.

HAprog: A New Prognostic Application to Assist Oncologists in Routine Care.

CONTEXT: More patients are seeing palliative care (PC) earlier in the disease trajectory. The Barretos Prognostic Nomogram (BPN) was designed to fill the gap of survival prognostication for patients with advanced cancer and months of life expectancy. However, its routine use is limited by the common need for a ruler and calculator. Additionally, the BPN requires blood tests. OBJECTIVES: The aim is to refine the BPN and to create a prognostic application (App) for use on smartphones. METHODS: This is a reanalysis of the two cohorts of advanced cancer patients (development, n=215 and validation, n=276). The variable 'metastasis' was revised (volume-site combinations) and 'KPS' replaced by 'ECOG-PS'. Prognostic variables were selected for multivariable Cox and Log-logistic parametric regression analyses; the most accurate final models were identified by backward variable elimination. Calibration and discrimination properties were evaluated in the validation sample. RESULTS: The 'full version' model is composed of 6 parameters: sex, locoregional disease, sites of metastasis, ECOG-PS, WBC and albumin. In the 'clinical version' model (5 variables), the variable 'antineoplastic treatment' was included and the laboratory variables were excluded. At validation, both models were well calibrated and presented adequate c-Index values (0.778 and 0.739). HAprog is a freely downloadable offline App that is used by clinicians to calculate prognosis in less than 1 minute. CONCLUSION: The new models that integrate HAprog are refined prognostic tools with adequate calibration and discrimination properties. It has potential practical impact for the oncologist dealing with outpatients with advanced cancer during the decision-making process.

BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer.

Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and tumorigenic capacity in the chick embryo choriallantoic membrane when compared to the parental cell line. These observations were supported by a significant increase in their stem cell frequency and by the enrichment for the breast cancer stem cell (BCSC) phenotype CD44+CD24-/low. Based on this data, the expression of BCSC markers (CD44, CD49f, P-cadherin, EpCAM, and ALDH1) was determined and found to be significantly enriched in breast cancer brain metastases when compared to primary tumors. Therefore, a brain (BR)-BCSC signature was defined (3-5 BCSC markers), which showed to be associated with decreased brain metastases-free and overall survival. Interestingly, this signature significantly predicted a worse prognosis in lymph node-positive patients, acting as an independent prognostic factor. Thus, an enrichment of a BCSC signature was found in brain metastases, which can be used as a new prognostic factor in clinically challenging breast cancer patients.

Impact of AferBio® on quality of life and chemotherapy toxicity in advanced lung cancer patients (AFERBIO study): protocol study for a phase II randomized controlled trial.

BACKGROUND: Lung cancer patients undergoing palliative chemotherapy exhibit many symptoms related to the disease, such as adverse events and infectious complications during treatment, which impacts directly their health-related quality of life (HRQOL). Nutritional status is a relevant aspect among advanced cancer patients under palliative care and food supplementation has the potential to reduce treatment-related adverse effects and improve the nutritional status. The product named AferBio® is a fermented supplement that has been described as able to provide some benefits, including the capacity to potentiate the effects of anticancer drugs, by promoting the reduction of side effects and ultimately improving HRQOL. METHODS/DESIGN: A Phase II double-blind placebo-controlled randomized clinical trial to assess the use of food supplementation with AferBio® in Stage IIIB or IV non-small cell lung cancer (NSCLC) patients beginning a second-line palliative mono-chemotherapy. The primary goal is to compare HRQOL scores between the arms of the study over time. The ten first patients included in the present study will undergo an AferBio®toxicity-testing (non-randomized phase). If no significant toxicity is found, the study will move on to the randomized phase. All patients will be randomized in blocks at a 1:1 ratio using the online tool REDCap. ECOG-PS (0-1 versus 2) criteria will be used for stratification. All patients included in the trial will be evaluated at baseline and at each chemotherapy cycle. Each evaluation will include the following: HRQOL (EORTC QLQ-C30, LC13 and IQualiV-Lung), ECOG-PS, anthropometric measurements, clinical and laboratory toxicity assessment and response evaluation. DISCUSSION: During palliative systemic therapy in advanced cancer patients, one of the main goals is the improvement and maintenance of HRQOL, which can be negatively affected by cancer symptoms, cancer- or treatment-related psychosocial difficulties, and chemotherapy toxicity. Thus, much research has been dedicated to the development of new and more effective and/or less toxic cancer therapies. The present study is justified by the testing of a novel food supplement that may reduce some toxicities, thus, having a potential positive impact on the HRQOL of lung cancer patients. The product in question (AferBio®) is already available for sale in Brazil, but has not yet been fully tested in cancer patients. TRIAL REGISTRATION: This Trial was registered on March 19, 2018 with ClinicalTrials.gov , NCT03469063. Protocol version: 2.0 from March 26, 2018. Trial status: Patient enrollment in the study began in April, 2018.

Development and validation of a prognostic nomogram for ambulatory patients with advanced cancer.

Predicting survival of advanced cancer patients (ACPs) is a difficult task. We aimed at developing and testing a new prognostic tool in ACPs when they were first referred to palliative care (PC). A total of 497 patients were analyzed in this study (development sample, n = 221; validation sample, n = 276). From 35 initial putative prognostic variables, 14 of them were selected for multivariable Cox regression analyses; the most accurate final model was identified by backward variable elimination. Parameters were built into a nomogram to estimate the probability of patient survival at 30, 90, and 180 days. Calibration and discrimination properties of the Barretos Prognostic Nomogram (BPN) were evaluated in the validation phase of the study. The BPN was composed of 5 parameters: sex, presence of distant metastasis, Karnofsky Performance Status (KPS), white blood cell (WBC) count, and serum albumin concentration. The C-index was 0.71. The values of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were 0.84, 0.74, and 0.74 at 30, 90, and 180 days, respectively. There were good calibration results according to the Hosmer-Lemeshow test. The median survival times were 313, 129, and 37 days for the BPN scores <25th percentile (<125), 25th to 75th percentile (125-175), and >75th percentile (>175), respectively (P < .001). The BPN is a new prognostic tool with adequate calibration and discrimination properties. It is now available to assist oncologists and palliative care physicians in estimating the survival of adult patients with advanced solid tumors.

Investigation Route of the Coronary Patient in the Public Health System in Curitiba, São Paulo and in Incor - IMPACT Study / Itinerário de Investigação do Paciente Coronariano do SUS em Curitiba, São Paulo e Incor - Estudo IMPACT

Background: The investigation of stable coronary artery disease (CAD) and its treatment depend on risk stratification for decision-making on the need for cardiac catheterization and revascularization. Objective: To analyze the procedures used in the diagnosis and invasive treatment of patients with CAD, at the Brazilian Unified Health System (SUS) in the cities of Curitiba, São Paulo and at InCor-FMUSP. Methods: Retrospective, descriptive, observational study of the diagnostic and therapeutic itineraries of the Brazilian public health care system patient, between groups submitted or not to prior noninvasive tests to invasive cardiac catheterization. Stress testing, stress echocardiography, perfusion scintigraphy, catheterization and percutaneous or surgical revascularization treatment procedures were quantified and the economic impact of the used strategies. Results: There are significant differences in the assessment of patients with suspected or known CAD in the metropolitan region in the three scenarios. Although functional testing procedures are most often used the direct costs of these procedures differ significantly (6.1% in Curitiba, 20% in São Paulo and 27% in InCor-FMUSP). Costs related to the procedures and invasive treatments represent 59.7% of the direct costs of SUS in São Paulo and 87.2% in Curitiba. In InCor-FMUSP, only 24.3% of patients with stable CAD submitted to CABG underwent a noninvasive test before the procedure. Conclusion: Although noninvasive functional tests are the ones most often requested for the assessment of patients with suspected or known CAD most of the costs are related to invasive procedures/treatments. In most revascularized patients, the documentation of ischemic burden was not performed by SUS. .

Fundamento: A investigação da doença arterial coronariana (DAC) estável e seu tratamento dependem da estratificação de risco para a decisão sobre a necessidade de cateterismo cardíaco e revascularização. Objetivo: Analisar os procedimentos utilizados no diagnóstico e tratamento invasivo dos pacientes com DAC do Sistema Único de Saúde (SUS) nos municípios de Curitiba, São Paulo e no IIncor- FMUSP. Métodos: Estudo retrospectivo, descritivo, observacional dos itinerários diagnósticos e terapêuticos dos pacientes do SUS, entre os grupos submetidos ou não a testes não invasivos prévios ao cateterismo cardíaco invasivo. Foram quantificados os procedimentos de teste ergométrico, ecocardiograma de estresse, cintilografia de perfusão, cateterismo e tratamento com revascularização percutânea ou cirúrgica e o impacto econômico destas estratégias utilizadas. Resultados: Existem diferenças importantes na avaliação do paciente com DAC suspeita ou conhecida nos três cenários. Apesar dos testes funcionais serem os procedimentos mais frequentemente utilizados, os custos diretos referentes a esses procedimentos diferem significativamente (6,1% em Curitiba, 20% em São Paulo e 27% no Incor-FMUSP). Os custos relacionados aos procedimentos e tratamentos invasivos representam 59,7% dos custos diretos do SUS em São Paulo e 87,2% em Curitiba. No Incor-FMUSP, apenas 24,3% dos pacientes com DAC estável submetidos à revascularização foram submetidos a um teste não invasivo antes do procedimento. Conclusão: Apesar dos testes funcionais não invasivos serem os exames mais frequentemente solicitados na avaliação de pacientes com DAC suspeita ou conhecida, a maior parte dos custos está relacionada a procedimento/tratamento ...

Investigation route of the coronary patient in the public health system in Curitiba, São Paulo and in InCor--IMPACT study.

BACKGROUND: The investigation of stable coronary artery disease (CAD) and its treatment depend on risk stratification for decision-making on the need for cardiac catheterization and revascularization. OBJECTIVE: To analyze the procedures used in the diagnosis and invasive treatment of patients with CAD, at the Brazilian Unified Health System (SUS) in the cities of Curitiba, São Paulo and at InCor-FMUSP. METHODS: Retrospective, descriptive, observational study of the diagnostic and therapeutic itineraries of the Brazilian public health care system patient, between groups submitted or not to prior noninvasive tests to invasive cardiac catheterization. Stress testing, stress echocardiography, perfusion scintigraphy, catheterization and percutaneous or surgical revascularization treatment procedures were quantified and the economic impact of the used strategies. RESULTS: There are significant differences in the assessment of patients with suspected or known CAD in the metropolitan region in the three scenarios. Although functional testing procedures are most often used the direct costs of these procedures differ significantly (6.1% in Curitiba, 20% in São Paulo and 27% in InCor-FMUSP). Costs related to the procedures and invasive treatments represent 59.7% of the direct costs of SUS in São Paulo and 87.2% in Curitiba. In InCor-FMUSP, only 24.3% of patients with stable CAD submitted to CABG underwent a noninvasive test before the procedure. CONCLUSION: Although noninvasive functional tests are the ones most often requested for the assessment of patients with suspected or known CAD most of the costs are related to invasive procedures/treatments. In most revascularized patients, the documentation of ischemic burden was not performed by SUS.