Laparoscopy assisted abomasal cannulation in cadavers of bovine fetuses.

BACKGROUND: Due to the complexity of ruminant digestion, cannulation of organs of the digestive tract has been carried out in order to advance the understanding of digestive physiology, nutrient degradability, gastrointestinal diseases and biotechnological research. The abomasal cannulation is interesting for nutritional studies, especially in suckling calves, to obtain fluid and abomasal content, evaluation of abomasal flow and function, and infusion of nutrients and drugs when it is intended to reach high concentrations in the organ. Conventionally, access and cannulation of digestive organs of ruminants has been performed by laparotomy, a method often criticized and classified as cruel by some sectors related to ethics and animal welfare. The aim of this present study is to describe and standardize a minimally invasive by laparoscopy assisted abomasal cannulation in bovine fetuses (cadavers), which had been previously slaughtered by accident and would be discarded in local slaughterhouses. RESULTS: The abomasal cannulation technique was feasible, simple and did not present major difficulties. The surgical time for cannulation of the abomasum, from the insertion of the trocars to the completion of the technique with fixation of the organ to the abdominal wall, ranged from 9 to 27 min, with an average of 15.5 ± 6.62 min. CONCLUSIONS: The Laproscopic assisted abomasal cannulation in bovine fetuses was feasible and safe with minimal tissue injury to the abdominal wall and with short surgical time. More studies in the clinical routine related to minimally invasive abomasal content collection, abomasopexy and abomasotomy are required in order to demonstrate its impact and importance in bovine clinic.

Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer.

BACKGROUND: KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. METHODS: CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. RESULTS: The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. CONCLUSIONS: KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

Socioeconomic status and retinoblastoma survival: Experience of a tertiary cancer center in Brazil.

BACKGROUND: Little is known about socioeconomic status (SES) and its effects in childhood cancer survival. This study aims to discuss the association between SES and survival of patients with retinoblastoma (RB) from a tertiary treatment center. PROCEDURE: A retrospective cohort study was conducted, including all patients with RB referred to the Brazilian National Institute of Cancer in Rio de Janeiro (January 2000-December 2016). RESULTS: Data from 160 patients were analyzed with mean age at diagnosis of 22.85 months (SD ± 14.29). Eighty-three patients (51.9%) had an interval to diagnosis equal to or longer than six months, and 13 children (8.1%) abandoned treatment. Five-year overall survival rate for all patients was 78.8% (95% CI, 72.4%-85.9%). In a multivariate model, patients whose fathers had more than nine years of study had a lower death risk. Patients from families having more than one child under five years had a 213% higher risk of death compared with those living with no other small child. Treatment abandonment also had a profound effect on death risk. CONCLUSION: Childhood cancer is notably important considering the potential years of life lost. RB has even more important elements, as the possibility of vision loss in cases with delayed diagnosis. Family characteristics seem to be highly related to RB survival, especially in low- and middle-income countries, where inequalities are still a public health issue. Strategies to improve survival should focus not only on large-scale settings such as improving national healthcare systems but also on more personalized actions that might help to mitigate disparities.

Next-generation sequencing of circulating tumor DNA for metastatic non-small cell lung cancer: a discussion on its implementation in the Brazilian clinical practice.

The objective of this review is to address the barriers limiting access to next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) for metastatic nonsquamous non-small cell lung cancer in Brazil and to propose its implementation in practice. A selected panel of lung cancer experts was provided with relevant prompts to address at a conference; a paper was then compiled on the topic. The authors propose specific and realistic recommendations for implementing access to ctDNA NGS. Further, the authors address all barriers and impediments mentioned within this review. There is a great need to increase ctDNA NGS for cancer care in Brazil. Adapting the current cancer testing framework is essential to expanding the use of this tool.

Patient-centered outcomes in non-small-cell lung cancer: a real-world perspective.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden - fatigue (p = 0.03), pain (p < 0.001) and arm pain (p = 0.022) - and worse global, social and physical functioning (all p < 0.001). In the first 2 years, most factors evolved to either improvement or stability: cough (p = 0.02), pain (p = 0.002), global functioning (p < 0.001) and emotional functioning (p < 0.001). Staging (p < 0.001), fatigue (p = 0.001) and gender (p = 0.004) were independently associated with overall survival. Conclusions: Our results demonstrate the feasibility of conducting real-world prospective analysis of patient-centered outcomes.

Lay abstract This study looked at patient-centered outcomes in lung cancer in a real-world setting. Standardized quality-of-life questionnaires were used to actively measure patients' perception of their functional well-being and health in a clinical setting. Three hundred thirty-seven patients were enrolled in a private cancer center in Brazil between 2014 and 2019. We demonstrated that patients diagnosed at advanced stages presented with more symptoms and lower capacity to perform daily activities. However, symptoms and functioning tended to improve during treatment. Our results show that it is possible to put patients at the heart of cancer care and use their experience to guide clinical approach.

Nonsecretory intestinocystoplasty: postoperative outcomes of 25 years.

OBJECTIVE: The objective of bladder augmentation (BA) is to create a low-pressure reservoir with adequate capacity. Despite its benefits, the use of intestinal patches in bladder enlargement provides a high risk of developing complications and BA with demucosalised bowel represents a potential alternative. Therefore, this study evaluated urological parameters and long-term clinical follow-up of patients submitted to nonsecretory BA in a single center with 25 years of experience. MATERIALS AND METHODS: Patients treated with BA underwent urological evaluation, which included history, physical examination and urodynamic study. The main urodynamic parameters (bladder capacity and bladder compliance) were assessed in the pre and postoperative moments, and compared by the Wilcoxon Signed Rank test. The main long-term complications were described. RESULTS: 269 patients (mean age 14±13 years, 47% male) underwent BA with the use of demucolised intestinal segments. Among the patients in the sample, 187 (69.52%) had neurogenic bladder, 68 (25.28%) had bladder exstrophy, nine had tuberculosis (3.34%), four had a posterior urethral valve (1.49%) and one with hypospadia (0.37%). After the surgical procedure, a significant increment in both urodynamic parameters was found, with a 222% increase in bladder capacity and 604% in bladder compliance (p < 0.001 in both analyzes). Mean follow-up time ranged from 2 to 358 months, with a median of 72 months (IQR 74-247). Among all patients, 5 presented spontaneous perforation. CONCLUSION: The study showed statistically signifi cant increase in both compliance and bladder capacity after non-secretory BA, with a low rate of severe complications.

The human endosalpinx: anatomical three-dimensional study and reconstruction using confocal microtomography.

PURPOSE: To evaluate in three dimensions (3D) the human endosalpinx and reconstruct its surface along its different anatomical segments, without the injection or insertion of luminal contrasts, using confocal microtomography (micro-CT). MATERIAL AND METHODS: 15 fallopian tubes (FT) from 14 women in reproductive age from procedures for benign disease or sterilization were selected. The specimens were fixed in formalin and stained with Lugol solution. Micro-CT studies were conducted on the specimens using protocols adapted from biological studies, to acquire images to reconstruct in 3D the endosalpinx surface. RESULTS: From these specimens, 6 presented the intra-mural segment, 14 presented the isthmus and 15 presented the ampulla and fimbria segment of the FT. The specimen presented tissue definition, and contrast sufficient for FT endosalpinx morphological analysis and lumen definition. The intramural portion presented initially a mucosal projection toward the lumen, bending on its own axis, and increased numbers of projections towards the isthmic portion, where the projections become longer more numerous. The endosalpinx becomes more tortuous, the lumen diameter increases and the mucosal projections become more bulky in the ampullary portion, with the projections less present on the antimesenteric side. The infundibular portion is marked with the organized and predictable endosalpinx, the abdominal ostium is cleared demonstrated, with the reduction of the endosalpinx volume. The fimbria demonstrated a small relation between fringes and intratubal endosalpinx. CONCLUSIONS: Microscopic anatomy of different segments of the human FT mucosa can be analyzed and reconstructed in 3D with histological correlation using micro-CT.

To Be Real or Virtual? That is the Question .

This editorial describes a crossroad that many plastic surgeons face when they have to decide how to manage their career. Level of Evidence V This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A wet dressing for male genital surgery: A phase II clinical trial.

PURPOSE: This study was to confirm the safety and efficacy of BC dressing when used in surgical male wound healing at the urogenital area. METHODS: Open, non-controlled clinical study of phase II. A total of 141 patients, among those children, adolescents and adults with hypospadias (112), epispadias (04), phymosis (13) and Peyronie's disease (12) that had a BC dressing applied over the operated area after surgery. A written informed consent was obtained from all participants. Study exclusion criteria were patients with other alternative treatment indications due to the severity, extent of the injury or the underlying disease. The outcomes evaluated were efficacy, safe and complete healing. The costs were discussed. RESULTS: In 68% patients, the BC dressing fell off spontaneously. The BC was removed without complications in 13% of patients at the outpatient clinic during the follow-up visit and 17% not reported the time of removal. In 3% of the cases, the dressing fell off early. Complete healing was observed between 8th and 10th days after surgery. The BC dressings have shown a good tolerance by all the patients and there were no reports of serious adverse events. CONCLUSION: The bacterial cellulose dressings have shown efficacy, safety and that can be considered as a satisfactory alternative for postoperative wound healing in urogenital area and with low cost.

Relationship between adherence to diet, glycemic control and cardiovascular risk factors in patients with type 1 diabetes: a nationwide survey in Brazil.

BACKGROUND: To determine the relationship between adherence to the diet reported by patients with type 1 diabetes under routine clinical care in Brazil, and demographic, socioeconomic status, glycemic control and cardiovascular risk factors. METHODS: This was a cross-sectional, multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data was obtained from 3,180 patients, aged 22 ± 11.8 years (56.3% females, 57.4% Caucasians and 43.6% non-Caucasians). The mean time since diabetes diagnosis was 11.7 ± 8.1 years. RESULTS: Overall, 1,722 (54.2%) of the patients reported to be adherent to the diet without difference in gender, duration of diabetes and socioeconomic status. Patients who reported adherence to the diet had lower BMI, HbA1c, triglycerides, LDL-cholesterol, non HDL-cholesterol and diastolic blood pressure and had more HbA1c at goal, performed more frequently self-monitoring of blood glucose (p < 0.001), and reported less difficulties to follow specific schedules of diet plans (p < 0.001). Less patients who reported to be adherent were obese or overweight (p = 0.005). The quantity of food and time schedule of the meals were the most frequent complaints. Logistic regression analysis showed that ethnicity, (Caucasians, (OR 1.26 [1.09-1.47]), number of medical clinical visits in the last year (OR 1.10 [1.06-1.15]), carbohydrate counting, (OR 2.22 [1.49-3.30]) and diets recommended by diabetes societies', (OR 1.57 [1.02-2.41]) were related to greater patients' adherence (p < 0.05) and age, [adolescents (OR 0.60 [0.50-0.72]), high BMI (OR 0.58 [0.94-0.98]) and smoking (OR 0.58 [0.41-0.84]) with poor patients' adherence (p < 0.01). CONCLUSIONS: Our results suggest that it is necessary to rethink medical nutrition therapy in order to help patients to overcome barriers that impair an optimized adherence to the diet.

Obesity may influence the relationship between sex hormones and lower urinary tract symptoms.

PURPOSE: The effects of serum testosterone in the lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) are not well established. The objective of the study is to evaluate the association of sex hormones with LUTS and control the results by patient weight. MATERIALS AND METHODS: The study comprised a cross-sectional analysis of 725 men included in a prostate cancer screening program at University of Sao Paulo Medical School. The serum concentrations of total testosterone (TT), free testosterone (FT) and sex hormone binding globulin (SHBG) were measured. Variables analyzed were age, American Urological Association (AUA) symptom score, storage symptoms, voiding symptoms, quality of life score, prostate specific antigen levels and prostate volume. Obesity was measured through the calculation of body mass index (BMI). A regression analysis model was performed. RESULTS: Median patient age was 65 years (48 to 94). A higher TT level was significantly associated with a severe AUA symptom score only among patients with a BMI ≥ 25. Median TT was 371, 370 and 427ng/dL (p = 0.017) in patients with mild, moderate and severe LUTS respectively. The multivariate regression analysis in patients with BMI ≥ 25 showed that only age, TT and sex score were related to LUTS. CONCLUSIONS: A higher TT is associated with a severe AUA score symptom index only in obese patients. Further analysis are necessary to evaluate the mechanisms through which testosterone may influence LUTS in these patients.

Expression of HOXA10 and HOXA11 in the endometrium of infertile patients with chronic endometritis.

OBJECTIVE: The study aimed to evaluate the impact of CE on the expression of HOXA10 and HOXA11 during the late proliferative phase in the endometrium of infertile women. METHODS: A prospective, translational cohort study was conducted in partnership with the Hospital Universitário Antônio Pedro in Niterói and the Clínica Ginendo in Rio de Janeiro after approval by the Ethics Committee. The patients were selected to participate in the study after showing an indication for hysteroscopy. All participants were divided into three groups: infertile women with endometritis (n=10), infertile women without endometritis (n=17) and fertile women without endometritis (n=10). At hysteroscopy, two endometrial samples were obtaneid, with one sent for histopathological examination per the gynecologist's request and the other used for immunohistochemistry procedures to evaluate the expression of CD138, HOXA10 and HOXA11. CD138 was used to confirm the diagnosis of CE. The analysis of HOXA10 and HOXA11 was performed using the HScoring method for immunohistochemistry with polyclonal antibodies. RESULTS: Women with and without endometritis had lower HOXA10 and HOXA11 expression values than women in the control group (fertile women without endometritis). CONCLUSIONS: The expression of HOXA10 and HOXA11 during the proliferative phase is not significantly different between infertile women with endometritis and infertile women without endometritis. Translational studies with a larger number of patients should be performed.

Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC-RELANCE/LACOG 0118.

Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC. Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant. Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43-37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57-31.73), and median progression-free survival was 11.23 months (95% CI: 10.70-12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only. Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.

A Single-Port, Multiple-Access, Custom-Made Device Used in Laparoscopically Assisted Cryptorchidectomy in Standing Horses-A Preliminary Study.

This study evaluates a new multiport device with single access to the abdominal cavity produced with routine hospital supplies that could be applied to laparoscopically assisted cryptorchidectomy in standing horses. Initially, the new device was evaluated on five cadavers of bovine fetuses (n = 5), placed assisted in a minilaparotomy performed in the flank region. Subsequently, the device was evaluated in four cryptorchid horses treated during the hospital routine. During the evaluation of the new device, the possibilities of exploring the abdominal cavity, inspection, and intra-abdominal manipulation with two Babcock forceps were verified. The possibilities were described, and surgical time data were recorded and analyzed using descriptive statistics. In the cadavers, a wide exploration of the abdominal cavity was possible, with a laparoscopic inspection through the right paralumbar fossa and manipulation of intra-abdominal structures with Babcock forceps inserted by the new device. In cryptorchid horses, laparoscopically assisted cryptorchidectomy with a new device was feasible in two patients, and in the others, it allowed the diagnosis of adhesions and ectopic locations in the inguinal region of testicles retained in the cavity. Therefore, the new device was efficient in exploring the inguinal region of cryptorchid horses in the standing position. The present study is preliminary and can support future studies that aim to improve the developed prototype.

The cost of type 1 diabetes: a nationwide multicentre study in Brazil.

OBJECTIVE: To determine the direct medical costs of type 1 diabetes mellitus (T1DM) to the National Brazilian Health-Care System (NBHCS) and quantify the contribution of each individual component to the total cost. METHODS: A retrospective, cross-sectional, nationwide multicentre study was conducted between 2008 and 2010 in 28 public clinics in 20 Brazilian cities. The study included 3180 patients with T1DM (mean age 22 years ± 11.8) who were surveyed while receiving health care from the NBHCS. The mean duration of their diabetes was 10.3 years (± 8.0). The costs of tests and medical procedures, insulin pumps, and supplies for administration, and supplies for self-monitoring of blood glucose (SMBG) were obtained from national and local health system sources for 2010-2011. Annual direct medical costs were derived by adding the costs of medications, supplies, tests, medical consultations, procedures and hospitalizations over the year preceding the interview. FINDINGS: The average annual direct medical cost per capita was 1319.15 United States dollars (US$). Treatment-related expenditure - US$ 1216.33 per patient per year - represented 92.20% of total direct medical costs. Insulin administration supplies and SMBG (US$ 696.78 per patient per year) accounted for 52.82% of these total costs. Together, medical procedures and haemodialysis accounted for 5.73% (US$ 75.64 per patient per year) of direct medical costs. Consultations accounted for 1.94% of direct medical costs (US$ 25.62 per patient per year). CONCLUSION: Health technologies accounted for most direct medical costs of T1DM. These data can serve to reassess the distribution of resources for managing T1DM in Brazil's public health-care system.

A wet dressing for hypospadias surgery.

INTRODUCTION: One of the main problems faced by surgeons involved in male genitalia surgeries, in particular in children with hypospadias, is the type of dressing and its use during the post-operatory period. MATERIALS AND METHODS: From a multidisciplinary project involving the use of sugarcane biopolymer membrane developed in the last 10 years, produced by bacterial action over sugarcane molasses, we developed a multiperforated pellicle that, when applied around the penis, protects the surgical field. It is a proven inert material that does not induce any reaction on the surgical field and can be left in situ maintaining the same characteristics during a long period of time without the need of replacement. This multiperforated tape can involve several times the penis shaft and due to its adhesiveness it hardly loosens. We compared the use of this dressing with a commercial one (made by polyurethane). Thirty patients with hypospadias were randomly selected for the use of this new type of dressing in the last 18 months. A similar group of patients used a similar commercial dressing made of polyurethane (Tegaderm) according to the same criteria of use. For safety reasons, we applied one or two sutures without the inclusion of the skin using an absorbable suture in order to prevent early detachment. A small gauze was left for 24 hours in order to absorb any possible bleeding. We recommended the irrigation of the dressing with water or saline at least three or four times a day and the patient was allowed to bath. The dressing did not need any special care and if not removed it usually detached spontaneously after 10 to 14 days. RESULTS: The tolerance to the material was satisfactory and there were no adverse reactions on the penile surface. In two cases of the biopolymer group the dressing detached spontaneously on the first and third days, respectively. In two cases of the polyurethane group it was observed major edema. The grade of satisfaction of the patients and their relatives was excellent on the biopolymer group. CONCLUSION: This dressing produced by a polysaccharide is a promising alternative for the treatment of children and adolescents submitted to genital surgery. Its main advantage is the possibility of several washes along the day without the need of any other manipulation.

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.

PURPOSE: The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non-small-cell lung cancer (mNSCLC). METHODS: Patients (n = 1,013) with EGFR/ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT. RESULTS: PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events. CONCLUSION: D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON).

OBJECTIVES: In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression. RESULTS: 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1. CONCLUSIONS: Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC.

EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.

PURPOSE: There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS: A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). CONCLUSION: This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.