Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. METHODS: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples. RESULTS: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD-L1 expression was categorized as PD-L1 negative (45.1%), PD-L1 positive low-expression 1%-49% (32.3%), and PD-L1 positive high-expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD-L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non-adenocarcinoma histology had a significantly higher median PD-L1 expression (p < 0.001). Additionally, PD-L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14-2.25, p < 0.01]). In the multivariate analysis, EGFR-positive tumors were more commonly associated with PD-L1 low expression (OR 0.62 [95% CI: 0.51-0.75], p < 0.01), while ALK-positive tumors had a significant risk of being PD-L1 positive (OR 1.81 [95% CI: 1.30-2.52], p < 0.01). CONCLUSIONS: PD-L1 expression was associated with well-defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD-L1 in patients with advanced NSCLC in a large Latin American cohort.

The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).

Breaking the unvirtuous cycle: barriers and opportunities for research and development in Paraguay. A case study.

Introduction: Medical research and development (R&D) is an undoubtedly relevant activity to drive innovation, improve healthcare policies and bring patients treatment opportunities for common and rare diseases. Equity and inclusion are matters of concern in research. High-income countries' research teams are more likely to have more impactful publications, grant funding, and clinical trials than middle or low-income countries. Low budget allocations to R&D and existing gaps in regulatory frameworks are some obstacles to growth. This unvirtuous cycle results in scarce advances in common endemic diseases and the underrepresentation of specific populations in innovative therapeutics research. Materials and methods: We conducted a policy review and qualitative research to determine the principal characteristics of basic and clinical medical research in Paraguay, as well as barriers and facilitators to improve innovative R&D strategies in this country. To this aim, we examined published articles from 2005 to 2020, the organizational structure of national research agencies, the current regulation framework, and the composition and experience of local research groups and ethical review boards (ERBs). In addition, we performed semi-structured interviews to evaluate perceptions and expectations from different stakeholders, including investigators, ERBs members, sponsor associates, and Regulatory Agency executive staff. Results: In 2018, Paraguay ranked 10th out of 12 South American countries in total number of publications and cumulative h-index score. Total Gross Domestic Product (GDP) allocation for R&D was 0.15%, ranking eighth out of 12 in the region. In 2021, the number of trials registered on ClinicalTrials.gov was 52, with only 16 ongoing recruiting studies at that time.Some of the main barriers identified included low incentives for academic careers and lack of experience in pharmaceutical research. An emergent necessity to develop a straight- forward normative framework was detected. Main facilitators included the development of two research initiative programs (PRONII and PROCIENCIA) from CONACYT (National Council of Science and Technology) which were associated with higher budget allocation and total number of publications in the 2011 to 2017 period. A total of six stakeholders participated in the semi-structured surveys. Interviewees highlighted the necessity of a centralized policy to promote R&D, which incorporates investigators and ERBs training, the development of standardized procedures, and the dissemination of research activities. Sponsor associates underlined that real-world evidence may represent a distinctive opportunity to enhance local research. Conclusion: Coordinated efforts are needed to break the unvirtuous cycle. There is an increasing interest in enhancing health research in Paraguay, materialized in the creation of specific programs that encourage the collaborative work of healthcare providers, basic scientists, and private investors. Nonetheless, a comprehensive approach is needed also to strengthen regulatory agencies and attract external sponsorship. While modern and currently popular topics, including artificial intelligence, real-world data, and translational research may represent key opportunities to seek investment, special policies should be adopted to prioritize research on the determinants of health in the Paraguayan population.

Generalized Lymphatic Anomaly as a Differential Diagnosis of Lytic Lesions.

Generalized lymphatic anomaly (GLA) is an infrequent multiorgan disease characterized by the presence of abnormal proliferation of lymphatic vessels. The diagnosis requires histological confirmation, and the treatment is controversial. We are presenting a case of a 28-year-old male patient who was diagnosed with an extragonadal mediastinal nonseminomatous germ cell tumor. He underwent chemotherapy, and during this treatment, radiologic findings evidenced lytic lesions. Multiple biopsies were performed, which revealed the presence of abnormal lymphatic vessels, characteristic of GLA. There are different etiologies of osteolytic lesions, and on some occasions, they mimic a tumoral entity. The clinical suspicion of GLA is the first step in approaching the diagnosis, particularly in young adult patients.

Short-course radiotherapy for rectal cancer: real-world evidence in Argentina.

Background: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management. Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment. Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. Results: In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02). Conclusion: In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.

Atypical pattern of response in rectal cancer after neoadjuvant pembrolizumab treatment: a case report, literature review, and proposed management model.

Background: Immunotherapy is the first-line treatment in patients with advanced microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC). Although immune checkpoint inhibitors (ICIs) for locally advanced rectal cancer (LARC) are not yet a standard, the results are very encouraging and raise the question of whether patients with clinical complete response (cCR) could receive nonoperative management (NOM). However, different patterns of response have challenged management strategies. Case Description: A 34-year-old woman diagnosed with dMMR LARC started treatment with capecitabine 2,000 mg/m2 on day 1 to 14 and oxaliplatin 130 mg/m2 on day 1 and every 21 days. Magnetic resonance imaging (MRI), performed three cycles later, showed local progression of the primary rectal lesion, which at that time had new peritoneal reflex involvement. A new hepatic lesion in segment V was observed. Due to disease progression, she was administered pembrolizumab 200 mg every 21 days. After three cycles, a discordant radiological response was observed on a new MRI scan that showed a complete response of the liver lesion and magnetic resonance tumor regression grade (mrTRG) 1 in the rectum. However, new involvement of the mesentery and enlargement of the regional lymph nodes (LNs) were also evident. A new colonoscopic biopsy was performed, showing no cancerous cells. She underwent surgery on the rectum and liver lesion. Pathology showed a complete response of the rectal wall and liver lesion, but 1 of 22 LNs was positive for adenocarcinoma (ypT0 N1 M0). The patient continued on pembrolizumab, and 14 months after surgery, she had not relapsed. Conclusions: Neoadjuvant immunotherapy for rectal cancer requires new recommendations for the assessment of clinical response. Pseudoprogression should be ruled out as an atypical response before deciding on surgical treatment. We propose an algorithm to address pseudoprogression in this setting.

Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report.

Limited strategies are available at disease progression on osimertinib for patients with EGFR-mutant NSCLC. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. In addition, loss of the EGFR T790M mutation has been mainly investigated as a resistance phenomenon to second-line osimertinib exposure. Remarkably, by studying the molecular profile at progression, it has been reported that the presence of the EGFR-sensitizing mutation, concurrently with the T790M, and C797S resulted in resistance to the current available EGFR tyrosine kinase inhibitors. Here, we report the first clinical evidence of gefitinib efficacy at EGFR exon 19 deletion/C797S mutation/T790M loss-mediated resistance to first-line osimertinib. Our findings highlight that dynamic genetic monitoring is a crucial approach in the evolution of EGFR-mutant NSCLC to understand the acquired molecular mechanisms for driving the best treatment strategy.

Current and novel therapeutic strategies for optimizing immunotherapy outcomes in advanced non-small cell lung cancer.

During the past decade, immunotherapy has dramatically improved the outcomes of patients with non-small cell lung cancer (NSCLC). The development of specific antibodies against the programmed death (PD1) receptor and its ligand PD-L1 (programmed death ligand-1) has demonstrated substantial efficacy in advanced NSCLC either in the first or in the second line. However, the success of immune checkpoint inhibitors (ICIs) as monotherapy did not reach all patients and long-term responders still represent a small subset of cases. Under these circumstances, different strategies have been and are being tested to optimize clinical outcomes. Here, we reviewed the current evidence and the more promising perspectives of ICI combination approaches, such as the addition of chemotherapy, antiangiogenic agents, other co-inhibitory or co-stimulatory checkpoints, and targeted therapies.

Implementation of a virtual multicenter gastrointestinal tumor board to reduce cancer disparities in Argentina.

Given the increasing complexity of cancer care, multidisciplinary tumor boards have become essential in daily clinical oncology practice. The Project Extension for Community Healthcare Outcomes (ECHO) initiative developed an innovative telementoring model using a "hub and spoke" design consisting of a team of experts (hub) that offers a full service to multiple participants (the spokes) during regularly scheduled sessions discussing patients' clinical cases. The Alexander Fleming Cancer Institute in Buenos Aires was the first hub in Latin America to implement Project ECHO for gastrointestinal tumors. In our 3-year experience, 80 patients from 37 centers were evaluated within Project ECHO and a range of three to five cases were discussed in each meeting. From our perspective, the impact of this novel approach was a remarkable strategy to reduce care disparities by equalizing access to high-quality medical knowledge in a multidisciplinary environment for medical discussions. Additionally, it was shown to have a cost-effective impact directly on the patients and the local health system, since relevant costs were saved after unnecessary treatments, studies and travel expenses were avoided.

Desmoid tumour in an inguinal hernia in a patient with a previous diagnosis of melanoma.

A 68-year-old man, without a family history of cancer, was treated for primary cutaneous melanoma of the scalp. Two years later, a right lateral cervical lymph recurrence was observed and he was treated with lymphadenectomy and adjuvant nivolumab for 1 year. Four years from the initial melanoma diagnosis, a computer tomography scan showed a solid nodular lesion of 26 × 40 × 75 mm inside the previously known inguinoscrotal hernia. A new recurrence of melanoma was the most probable diagnosis and a right inguinal hernioplasty was performed. Notably, the histopathological examination revealed a mesenteric fibromatosis with the typical immunohistochemical pattern (strong nuclear staining of ß-catenin). Interestingly, this represents the first case of a patient with a mesenteric desmoid tumour presenting as an inguinal hernia masking a cutaneous melanoma recurrence.

Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP).

INTRODUCTION: Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M mutations and evidence of relapse of the disease. Effectiveness and safety of this drug have been studied in multiple clinical trials and observational studies, however, information regarding outcomes among Hispanic patients treated with Osimertinib is scarce. The objective of this study was to examine real-world effectiveness and safety of first-line Osimertinib in a cohort of Hispanic patients with NSCLC, emphasizing post-progression outcomes. METHODS: This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC. Patients with a confirmed diagnosis of metastatic EGFR-mutated NSCLC who received Osimertinib (80mg/day until evidence of disease progression or presence of intolerable adverse effects) were identified and included. NGS was performed in tumor samples or liquid biopsies among patients who had disease progression. The primary outcome was progression-free survival, and the secondary outcome was post-progression survival. RESULTS: A total of 94 patients from Mexico, Argentina, Costa Rica, Colombia, Panama, Chile and the USA were included, with a median age of 59 years. Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4-18.2 months). Lung/pleura and lymph nodes were the most common sites of progression. Median post-progression survival was 7.73 months (95%CI 4.07 months-Not reached). Factors which negatively affected PFS included presence of liver metastases at diagnosis and a tumor mutational burden > 5 mut/Mb. CONCLUSION: Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC. Liver metastases and a higher tumor mutation burden were associated with a lower PFS. Despite effectiveness, different mechanisms of resistance were identified among the patients in this cohort, including mutations which can be targeted by other therapeutic options.

Assessing the methodological quality of quality-of-life analyses in first-line non-small cell lung cancer trials: A systematic review.

BACKGROUND: Non-cytotoxic therapy has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients. With unique mechanisms of action, these agents have decidedly improved survival and have demonstrated an improved toxicity profile. However, the real-life experience of the patient, which is commonly assessed by health-related quality of life (HRQoL) measurement, is not clearly established with this new generation of lung cancer treatments. The heterogeneity created by specific patient subgroups and different therapeutics calls for a tailored-approach to analyzing patient-reported outcomes. The objective of this systematic review was to assess the methodological quality of HRQoL analysis in Randomized Clinical Trials (RCTs) involving biologic agents to treat NSCLC. METHODS: A systematic literature search was performed using Medline, Embase, and Web of Science databases to identify NSCLC RCTs published between January 1st, 2000 and January 1st, 2020 reporting HRQoL measures. Only RCTs that both enrolled previously untreated patients with advanced NSCLC and had HRQoL analysis were included. RESULTS: 4203 abstracts were screened, of which only 85 RCTs met inclusion and exclusion criteria for analysis. The most applied HRQoL assessment tools were the EORTC-QLQ-C30 (47, 55.3 %), and EORTC-QLQ-LC13 (35, 41.2 %). The median number of verified CONSORT-PRO Extension criteria in the included trials was 3, and only in 10 (11.8 %) trials were all criteria well-documented. Notably, only 21 (24.7 %) RCTs performed subgroup analyses to specifically evaluate HRQoL in different patient populations. CONCLUSION: QoL reporting in clinical trials is inconsistent and the quality of QoL measures adopted in a majority of trials is suboptimal. Considering the fact that NSCLC is a biologically diverse disease and that the treatments differ based on patient and tumor-specifics, efforts should be pursued to tailor QoL measures for different subsets of this patient population in addition to mandating QoL reporting in clinical trials. We believe that this is necessary to understand the real-life experience of lung cancer patients in the era of personalized medicine.

First-line cisplatin, docetaxel, and cetuximab for patients with recurrent or metastatic head and neck cancer: A multicenter cohort study.

BACKGROUND: The targeted therapy cetuximab [directed at the epidermal growth factor receptor (EGFR)] in combination with 5-fluorouracil and platinum-based chemotherapy (the EXTREME regimen) has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Thus, this scheme has been established as the preferred first-line option for these patients. However, more recently, a new strategy combining platinum, taxanes, and cetuximab (the TPEx regimen) has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials. AIM: To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study. METHODS: This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1, 2017 and April 31, 2020. Chemotherapy consisted of four cycles of docetaxel, cisplatin, and cetuximab followed by cetuximab maintenance therapy. Clinical outcomes and toxicity profiles were collected from medical charts. Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors (version 1.1). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Twenty-four patients were included. The median age at diagnosis was 58 years (range: 36-77 years). The majority of patients (83.3%) received at least four chemotherapy cycles in the initial phase. In the included group, the overall response rate was 62.5%, and 3 patients achieved a complete response (12.5%). The median time to response was 2.4 mo [95% confidence interval (CI): 1.3-3.5]. With a median follow-up of 12.7 mo (95%CI: 8.8-16.6), the median progression-free survival (PFS) was 6.9 mo (95%CI: 6.5-7.3), and the overall survival rate at 12 mo was 82.4%. Patients with documented tumor response showed a better PFS than those with disease stabilization or progression [8.5 mo (95%CI: 5.5-11.5) and 4.5 mo (95%CI: 2.5-6.6), respectively; P = 0.042]. Regarding the safety analysis, two-thirds of patients reported at least one treatment-related adverse event, and 25% presented grade 3 toxicities. Of note, no patient experienced grade 4 adverse events. CONCLUSION: TPEx was an adequately tolerated regimen in our population, with low incidence of grade 3-4 adverse events. The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination. This regimen may be considered an attractive therapeutic strategy due to its simplified administration, decreased total number of chemotherapy cycles, and treatment tolerability.

Cyclin-Dependent Kinase 4/6 Inhibitor Outcomes in Patients With Advanced Breast Cancer Carrying Germline Pathogenic Variants in DNA Repair-Related Genes.

PURPOSE: In recent years, unprecedented benefits have been observed with the development of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. However, there is scarce evidence of their value in specific populations, such as patients carrying germline pathogenic variants in DNA repair-related genes. PATIENTS AND METHODS: We retrospectively studied the efficacy of CDK 4/6 inhibitors plus endocrine therapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Three cohorts were compared, including patients harboring germline pathogenic variants in DNA repair-related genes (gBRCA1/2-ATM-CHEK2 mutated), those tested without these mutations (wild type [WT]), and the nontested subgroup. Relevant prognostic factors including age, metastatic site (visceral v nonvisceral), Eastern Cooperative Oncology Group, and prior treatment with CDK 4/6 inhibitors were stratified by univariate and multivariate Cox regression models. RESULTS: Among the total population (n = 217), 15 (6.9%) patients carried gBRCA1/2 (n = 10)-ATM (n = 4)-CHEK2 (n = 1) pathogenic variants, 45 (20.7%) were WT, and 157 (72.4%) were nontested. Gene pathogenic variant carriers were younger (P < .001). Most patients (164, 75.6%) had not received prior endocrine therapy in the advanced setting. Median progression-free survival was shorter in patients with evaluated germline pathogenic variants (10.2 months [95% CI, 5.7 to 14.7]), compared with WT and nontested patients (15.6 months [95% CI, 7.8 to 23.4], and (17.6 months [95% CI, 12.9 to 22.2]; P = .002). Consistently, a worse median overall survival was observed in the subgroup with germline pathogenic variants than in the WT group (P = .006). Multivariable analysis showed that mutation status was an independent prognostic factor of progression-free survival (P = .020) and overall survival (P = .012). CONCLUSION: In this retrospective real-world study, gBRCA1/2-ATM-CHEK2 pathogenic variants were independently associated with poor outcomes in patients with advanced breast cancer treated with CDK4/6 inhibitors.

Appraising the quality of meta-analysis for breast cancer treatment in the adjuvant setting: A systematic review.

INTRODUCTION: Breast cancer is the tumor with highest incidence in women worldwide and adjuvant treatment is extremely important to achieve disease control. Given the relevance of systematic reviews, their rigor should be warranted to avoid biased conclusions. Our objective was to investigate the methodological quality of meta-analysis of early breast cancer adjuvant treatment. MATERIAL AND METHODS: Comprehensive searches were performed using electronic databases from 1/1/2007 to 11/12/2018. All studies identified as a systematic review with meta-analysis investigating the efficacy of breast cancer adjuvant treatments were included. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility. Quality was assessed using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) version 2 tool. RESULTS: Of 950 citations retrieved, 66 studies (7.0%) were deemed eligible. Methodological quality was highly variable, median AMSTAR score 8.5 (IQR 7-9.5) and range 0-16. There was a weak positive correlation between journal impact factor and AMSTAR score (r = 0.17) and citation rate and AMSTAR score (r = 0.16). Cochrane Systematic Reviews were of higher quality than reviews from other journals. Overall confidence was critically low for 61 (92.4%) studies, and the least well-reported domains were the statement of conflict of interest and funding source for the included studies (4.6%), the report of a pre-defined study protocol (15.2%), and the description of details of excluded studies (6.1%). CONCLUSIONS: Our findings reinforce concerns about the design, conduction and interpretation of meta-analysis in current literature. Methodological quality should be carefully considered and journal editors, decision makers and readers in general, must follow a critical approach to this studies.

Analysis of adverse events attribution and reporting in cancer clinical trials: A systematic review.

We systematically reviewed the quality of AEs reports in published oncology trials analyzing also the bias in the attribution process. We searched MEDLINE, PubMed (2000-2019) selecting randomized, double-blind, placebo-controlled, and phase 3 cancer trials using exclusively targeted therapy or immunotherapy-related drugs. The proportion of publications with complete AE reports (including both all-cause and drug-related AE data) and the AEs attribution ratio (patients with drug-related over all-cause AE) were investigated. Among 60 trials (38,174 patients) included, 40 (66.6 %) presented an incomplete report of AEs attribution. Journals with the lowest impact factor were significantly associated with deficient reports of grade 3-4 AEs (p = 0.02). Under placebo administration, the median incidence of all-grade drug-related AEs was 49 % (IQR 39-56). The median attribution ratio for all-grade AEs in the active and placebo arms was 88.9 % (IQR 79.8-93) and 53.9 % (IQR 43.4-60.9), respectively. The AEs reporting and attribution process appear to be more unreliable than expected.

Characteristics and outcomes of thymomas in Latin America: Results from over 10 years of experience (CLICaP-LATimus).

BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.

Mentoring as an opportunity to improve research and cancer care in Latin America (AAZPIRE project).

Effective networking and mentoring are critical determinants of professional satisfaction and success in oncology. There are multiple benefits associated with established mentoring programs. However, these are scarce in Latin America (LATAM). The AAZPIRE project meeting was held to encourage the discussion of mentorship strategies in our region, to create new learning frameworks, and improve cancer care. A group of 30 young oncologists and investigators, together with seven members of LACOG and CLICaP experts of 8 LATAM countries, were reunited to share views and define opportunities, barriers, and possible solutions to implement mentorship programs in LATAM. For each of the mentioned topics, key points were obtained by consensus, and a literature review was conducted to support group conclusions. This article analyses mentoring in LATAM countries and its role on promoting leadership. It will address conceptual frameworks, limitations, and opportunities from the perspectives of both mentor and mentee. The creation of regional and international group stimulation programs and joint projects that impact health policies are attractive, starting points to implement mentorship scenarios.

Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives.

Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs-not associated with classical V600E/K BRAF mutations-malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.