Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

A plain language summary of the CheckMate 649 study: nivolumab in combination with chemotherapy compared to chemotherapy alone for untreated advanced or metastatic cancer of the stomach or esophagus.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of the 1-year results of a clinical research study known as CheckMate 649 published in The Lancet in June 2021. The 2-year results on the participants' health and overall quality of life from the same study are in a second publication in Nature in March 2022. Until recently, chemotherapy was the only first treatment option for people with advanced or metastatic gastroesophageal adenocarcinoma who had not been treated before. Patients receiving chemotherapy lived on average for less than 1 year. Nivolumab is an immunotherapy that works by activating a person's immune system to fight back against cancer cells. The goal of CheckMate 649 was to find out if the combination of nivolumab and chemotherapy would help patients with advanced or metastatic gastroesophageal adenocarcinoma live longer and without their cancer getting worse. WHAT WERE THE RESULTS?: Results from the final analysis are reported here. Of 1581 people who took part in the study, 789 received nivolumab and chemotherapy and 792 received chemotherapy. Researchers found that, on average, participants who received nivolumab and chemotherapy lived longer overall than those who received chemotherapy alone. The length of time participants lived without their cancer getting worse was also longer on average with nivolumab and chemotherapy than chemotherapy treatment alone. However, more participants in the nivolumab and chemotherapy group had side effects than those in the chemotherapy group. The three most common side effects in both types of treatment were nausea (urge to vomit), diarrhea and peripheral neuropathy. Participants who received nivolumab and chemotherapy had a lower risk of their cancer symptoms worsening and reported that they were 'less bothered' from side effects of treatment than those receiving chemotherapy alone. WHAT DO THE RESULTS MEAN?: The nivolumab and chemotherapy combination is considered a new standard treatment option and is approved in several countries as a treatment for adults who have not been treated before for their advanced or metastatic gastroesophageal cancer based on results from CheckMate 649. Clinical Trial Registration: NCT02872116 (ClinicalTrials.gov).

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.

BACKGROUND: First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone. METHODS: In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116. FINDINGS: From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified. INTERPRETATION: Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients. FUNDING: Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.

Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer.

BACKGROUND: Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC. MATERIALS AND METHODS: Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis. RESULTS: Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor. CONCLUSION: Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.

Impact of COVID-19 Infection on Patients with Cancer: Experience in a Latin American Country: The ACHOCC-19 Study.

INTRODUCTION: The ACHOCC-19 study was performed to characterize COVID-19 infection in a Colombian oncological population. METHODOLOGY: Analytical cohort study of patients with cancer and COVID-19 infection in Colombia. From April 1 to October 31, 2020. Demographic and clinical variables related to cancer and COVID-19 infection were collected. The primary outcome was 30-day mortality from all causes. The association between the outcome and the prognostic variables was analyzed using logistic regression models and survival analysis with Cox regression. RESULTS: The study included 742 patients; 72% were >51 years. The most prevalent neoplasms were breast (132, 17.77%), colorectal (92, 12.34%), and prostate (81, 10.9%). Two hundred twenty (29.6%) patients were asymptomatic and 96 (26.3%) died. In the bivariate descriptive analysis, higher mortality occurred in patients who were >70 years, patients with lung cancer, ≥2 comorbidities, former smokers, receiving antibiotics, corticosteroids, and anticoagulants, residents of rural areas, low socioeconomic status, and increased acute-phase reactants. In the logistic regression analysis, higher mortality was associated with Eastern Cooperative Oncology Group performance status (ECOG PS) 3 (odds ratio [OR] 28.67; 95% confidence interval [CI], 8.2-99.6); ECOG PS 4 (OR 20.89; 95% CI, 3.36-129.7); two complications from COVID-19 (OR 5.3; 95% CI, 1.50-18.1); and cancer in progression (OR 2.08; 95% CI, 1.01-4.27). In the Cox regression analysis, the statistically significant hazard ratios (HR) were metastatic disease (HR 1.58; 95% CI, 1.16-2.16), cancer in progression (HR 1.08; 95% CI, 1.24-2.61) cancer in partial response (HR 0.31; 95% CI, 0.11-0.88), use of steroids (HR 1.44; 95% CI, 1.01-2.06), and use of antibiotics (HR 2.11; 95% CI, 1.47-2.95). CONCLUSION: In our study, patients with cancer have higher mortality due to COVID-19 infection if they have active cancer, metastatic or progressive cancer, ECOG PS >2, and low socioeconomic status. IMPLICATIONS FOR PRACTICE: This study's findings raise the need to carefully evaluate patients with metastatic cancer, in progression, and with impaired Eastern Cooperative Oncology Group status to define the relevance of cancer treatment during the pandemic, consider the risk/benefit of the interventions, and establish clear and complete communication with the patients and their families about the risk of complications. There is also the importance of offering additional support to patients with low income and residence in rural areas so that they can have more support during cancer treatment.

Low Prevalence of the Four Common Colombian Founder Mutations in BRCA1 and BRCA2 in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer.

BACKGROUND: Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population. MATERIALS AND METHODS: Screening for the four Colombian founder mutations BRCA1/c.3331_3334delCAAG, BRCA1/c.5123C>A, BRCA2/c.2806_2809delAAAC, and BRCA2/c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR-based restriction fragment length polymorphism analysis, and qualitative real-time PCR. Mutations were confirmed by direct DNA sequencing. RESULTS: The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years. CONCLUSION: Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro-Colombian population. IMPLICATIONS FOR PRACTICE: Risk reduction intervention programs are needed for women who are found to carry a BRCA1/2 mutation, as is the implementation of prevention programs for patients with inherited breast cancer, to reduce the burden of inherited diseases. With the aim of reducing racial disparities in breast cancer prevention, this study focused on genetic testing and treatment for patients in a minority population with BRCA1/2 mutations.

Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter.

Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-ß induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

Advanced Breast Cancer Guidelines in Latin America: Assessment, Adaptation, and Implementation of Fifth Advanced Breast Cancer Consensus Guidelines.

PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.

First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.

Impact of vaccination against COVID-19 on patients with cancer in ACHOC-C19 study: Real world evidence from one Latin American country.

Introduction: During the pandemic, it has been recommended that vaccination against COVID-19 be a priority for patients with cancer; however, these patients were not included in the initial studies evaluating the available vaccines. Objective: To define the impact of vaccination against COVID-19 in preventing the risk of complications associated with the infection in a cohort of patients with cancer in Colombia. Methods: An analytical observational cohort study, based on national registry of patients with cancer and COVID 19 infection ACHOC-C19, was done. The data was collected from June 2021, until October 2021. Inclusion criteria were: Patients older than 18 years with cancer diagnosis and confirmed COVID-19 infection. Data from the unvaccinated and vaccinated cohorts were compared. Outcomes evaluated included all-cause mortality within 30 days of COVID-19 diagnosis, hospitalization, and need for mechanical ventilation. The estimation of the effect was made through the relative risk (RR), the absolute risk reduction (ARR) and the number needed to treat (NNT). Multivariate analysis was performed using generalized linear models. Results: 896 patients were included, of whom 470 were older than 60 years (52.4%) and 59% were women (n=530). 172 patients were recruited in the vaccinated cohort and 724 in the non-vaccinated cohort (ratio: 1 to 4.2). The cumulative incidence of clinical outcomes among the unvaccinated vs vaccinated patients were: for hospitalization 42% (95% CI: 38.7%-46.1%) vs 29%; (95% CI: 22.4%-36.5%); for invasive mechanical ventilation requirement 8.4% (n=61) vs 4.6% (n=8) and for mortality from all causes 17% (n=123) vs 4.65% (n=8). Conclusion: In our population, unvaccinated patients with cancer have an increased risk of complications for COVID -19 infection, as hospitalization, mechanical ventilation, and mortality. It is highly recommended to actively promote the vaccination among this population.

Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649.

PURPOSE: In CheckMate 649, first-line nivolumab plus chemotherapy prolonged overall survival versus chemotherapy in patients with advanced/metastatic non-human epidermal growth factor receptor 2 (HER2)-positive gastric/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC). We present exploratory patient-reported outcomes (PROs). METHODS: In patients (N = 1,581) concurrently randomly assigned 1:1 to nivolumab plus chemotherapy or chemotherapy and in those with tumor PD-L1 expression at a combined positive score (CPS) of ≥5, health-related quality of life (HRQoL) was assessed using the EQ-5D and Functional Assessment of Cancer Therapy-Gastric (FACT-Ga), which included the FACT-General (FACT-G) and Gastric Cancer subscale (GaCS). The FACT-G GP5 item assessed treatment-related symptom burden. Longitudinal changes in HRQoL were assessed using mixed models for repeated measures in the PRO analysis population (randomly assigned patients with baseline and ≥1 postbaseline assessments). Time to symptom or definitive deterioration analyses were also conducted. RESULTS: In the PRO analysis population (n = 1,360), PRO questionnaire completion rates were mostly >80% during treatment. Patient-reported symptom burden was not increased with nivolumab plus chemotherapy versus chemotherapy. Mean improved changes from baseline were greater with nivolumab plus chemotherapy versus chemotherapy for FACT-Ga total, GaCS, and EQ-5D visual analog scale in patients with a CPS of ≥5; results were similar for the overall PRO analysis population. In CPS ≥5 and all randomly assigned populations, nivolumab plus chemotherapy reduced the risk of symptom deterioration versus chemotherapy, on the basis of FACT-Ga total score and GaCS; time to definitive deterioration was longer, and the risk of definitive deterioration in HRQoL was reduced with nivolumab plus chemotherapy across EQ-5D and most FACT-Ga measures (hazard ratio [95% CI] <1). CONCLUSION: Compared with chemotherapy alone, first-line nivolumab plus chemotherapy showed stable or better on-treatment HRQoL in patients with advanced/metastatic non-HER2-positive GC/GEJC/EAC and also showed decreased risk of definitive HRQoL deterioration.

Two Unusual Mutations in the Epidermal Growth Factor Receptor Gene in a Patient With Lung Adenocarcinoma.

Adenocarcinoma (ADC) of the lung is the most frequent pathology corresponding to non-small cell lung cancer (NSCLC). The advent of target therapy and the discovery of drugs that block signaling pathways related to cellular events involved in the progression of the disease have led to a better prognosis in cases of ADC. Some of the targeted therapy focuses on the blockade of epidermal growth factor receptor (EGFR), targeting mutations in exon 19 and 21, with favorable clinical outcomes. However, there is limited evidence with respect to unusual mutations as in exon 18 (g719x) and 20 (s768). In this report, we present a case of a 65-year-old female with two unusual mutations in the EGFR gene, in exon 18 (g719x) and 20 (s768i), without central nervous system (CNS) involvement; these mutations are typically resistant to standard therapy. We decided to administer osimertinib because of its favorable toxicity profile and with a view to preventing future CNS relapse.

Peripheral Neural Sheath Breast Sarcoma: Case Report and Literature Review.

Primary sarcomas of the breast are heterogeneous neoplasms derived from the non-epithelial elements of the mammary gland. Malignant peripheral nerve sheath tumors comprise 5-10% of all malignant soft tissue sarcomas. Its heterogeneity and low incidence (1 in 100,000) limit the performance of prospective studies. Therefore, most published articles include individual reports and case series with a small number of patients, making it impossible to determine clear treatment standards in this scenario. A 36-year-old young woman with no personal history consulted the National Cancer Institute of Colombia with a 1-year progression of a rapidly growing mass in her left breast until reaching an approximate tumor size of 20 × 20 cm. Histopathological analysis with a tru-cut biopsy taken from the lesion revealed the presence of a breast sarcoma with positive staining for SOX-10 and S-100. A radical mastectomy as her first treatment included the resection of a costal arch and, therefore, the reconstruction of the chest wall with coverage of the defect with an extended latissimus dorsi flap followed by consolidation therapy with adjuvant radiotherapy (RT) and chemotherapy. Evidence regarding malignant peripheral nerve sheath sarcoma of the breast treatment corresponds to retrospective analyses and case reports with high heterogeneity and variability about strategies in surgical procedures and adjunctive therapy such as complementary chemotherapy and RT; therapeutic approach should always include a multidisciplinary team.

Adult Wilms' Tumor: Case Report and Literature Review.

Wilms' tumor is childhood's most common renal tumor, and its presentation in the adult age is extremely rare. Due to the low frequency in adults, no standard management guidelines are available for this population, also the natural history of the disease and management is unclear. We present a case report of a 31-year-old woman with metastatic Wilms' tumor, with lymph node, lung and liver involvement; systemic treatment with chemotherapy was started, with complete clinical response. Finally, a literature review is performed to showcase the differences in the clinical course, prognosis, and treatment alternatives, in adult disease compared to childhood.

Tumor-to-Tumor Metastasis: Lung Adenocarcinoma as a Recipient of Metastasis from Renal Cell Carcinoma: A Case Report.

BACKGROUND The occurrence of metastasis from one neoplasm to another is known as tumor-to-tumor metastasis (TTM). It is a rare phenomenon in the natural history of any neoplasm, with approximately 100 cases reported in the literature to date. The lungs are the most frequent metastatic tumor donors and kidney cancer is the most common recipient. However, the opposite phenomenon (lung adenocarcinoma as a recipient of metastasis from renal carcinoma) has not been previously reported in the literature. CASE REPORT We present the case of a man with a history of multiple neoplasms. He had a diffuse large B-cell lymphoma in 2006, a left papillary renal cell carcinoma (RCC) type 2 in 2006, and an acinar adenocarcinoma of the prostate in 2011. A follow-up computed tomography scan in July 2019 showed a suspicious lung nodule on the left upper lobe and a retroperitoneal hypermetabolic mass on the positron emission tomography scan. The lung nodule and retroperitoneal mass biopsies were consistent with a primary lung adenocarcinoma with a lepidic pattern and a metastatic RCC, respectively. In January 2020, he underwent a thoracoscopic left upper lobectomy and a mediastinal lymph node dissection. Histopathological evaluation revealed a 2-cm nodule composed of a lung adenocarcinoma with an intratumoral metastasis from a papillary RCC. To date, the patient has stable renal neoplastic metastatic disease and no locoregional recurrences of the lung adenocarcinoma. CONCLUSIONS Metastasis from one primary tumor to another primary tumor is an extremely unusual event. We report one of the first cases of an RCC metastasis to a primary lung adenocarcinoma.

Hyperprogression in Pediatric Melanoma Metastatic to the Breast Treated with a Checkpoint Inhibitor.

Metastatic melanomas in the pediatric population are rare, but they have been appearing more frequently. Unfortunately, little is known about the differences in the biology and therapeutic implications of pediatric metastatic melanomas when compared to those found in adults. Herein, we have presented the case of a 13-year-old girl with a stage IIID malignant melanoma arising from a congenital nevus. This patient underwent surgical management, and she received adjuvant interferon therapy; however, this treatment was incomplete due to a grade 3 transaminase elevation and the early recurrence of the disease. An isolated metastasis to the breast was documented, and a mastectomy was performed. Soon afterward, low-volume lung metastases developed, and she was treated with nivolumab. After two treatment cycles, the disease continued to develop in a hyperprogressive manner. Advances in the characterization and understanding of pediatric melanomas are needed, as well as experience in the management of new therapies in these cases, which would help clarify the extent to which we can extrapolate the data obtained from the adult population. Therapeutic interventions in melanoma cases are evolving rapidly, and the role of metastasectomies in the era of immunotherapy and BRAF and MEK-targeted therapies is largely unknown. Moreover, the identification of risk factors for the development of hyperprogression and its underlying mechanisms are also warranted.

Características de los pacientes con cáncer de pulmón de célula no pequeña en el Instituto Nacional de Cancerología de Colombia / Characteristics of patients with non-small cell lung cancer at the National Cancer Institute of Colombia

Resumen Objetivos: Describir las características demográficas, histopatológicas, biología molecular tumoral y estadificación de los pacientes con cáncer de pulmón de célula no pequeña atendidos entre diciembre de 2013 y diciembre de 2018 en el Instituto Nacional de Cancerología de Colombia. Métodos: Estudio descriptivo de corte transversal. Resultados: Se incluyeron 392 pacientes con cáncer de pulmón de célula no pequeña, la mediana de edad fue 65.9 años (rango, 28,9 a 88,9 años). 198 (50,5%) pacientes fueron mujeres, obteniendo una relación hombre mujer 1:1. El 90.6% de los casos eran mayores de 50 años. Antecedente de tabaquismo se presentó en 211 (53,8%) pacientes, 75.8% de la población masculina y 32,3% de la población femenina eran fumadores. El adenocarcinoma se encontró en 293 (74,7%) pacientes y el carcinoma escamocelular en 73 (18,6%) pacientes. La estadificación patológica fue: estadio I en 22 (5,6%) pacientes, estadio II en 18 (4,6%), estadio III en 40 (10,2%) pacientes, estadio IV en 311 (79,3%) pacientes y no hubo dato en un solo paciente. Se detectó la mutación del EGFR en 21,2% de los pacientes. Los reordenamientos de ALK se identificaron en 4,6% de los pacientes y el PDL 1 solo se midió en el 9% de la población. Conclusiones: este estudio nos muestra el panorama general del cáncer de pulmón de célula no pequeña en la población colombiana, en donde la mayoría de los pacientes se diagnostican en estadios avanzados de la enfermedad y nos expone la necesidad de nuevas estrategias para la detección temprana y el acceso oportuno de los pacientes con cáncer de pulmón.

Abstract Objectives: to describe the demographic and histopathologic characteristics, tumor molecular biology and staging of patients with non-small cell lung cancer treated between December 2013 and December 2018 at the National Cancer Institute of Colombia. Methods: a retrospective cohort study based on data from medical records. Results: 392 patients with non-small cell lung cancer were included. The median age was 65.9 years (range: 28.9 to 88.9 years); 198 (50.5%) patients were women, obtaining a 1:1 male-female ratio. 90.6% of the cases were older than 50 years. History of smoking occurred in 211 patients (53.8%), 75.8% of the male population and 32.3% of the female population were smokers. Adenocarcinoma was found in 293 (74.7%) patients, while squamous cell carcinoma was present in 73 (18.6%) patients. The pathological staging was: 22 (5.6%) patients were in stage I, 18 (4.6%) had stage II, 40 (10.2%) patients were in stage III, stage IV was found in 311 (79.3%) patients, and there was no data in one patient. EGFR mutation was detected in 21.2% of patients. ALK rearrangements were identified in 4.6% of patients and PDL-1 was only found in 9% of the population. Conclusions: this study presents a general panorama of non-small cell lung cancer in the Colombian population, where most patients are diagnosed in advanced stages of the disease, and highlights the need for new strategies for early detection and better access for patients with lung cancer.

Malignant solitary fibrous tumor of the kidney: report of the first case managed with interferon.

Solitary fibrous tumors of the kidney are extremely rare tumors with unpredictable behavior. We describe a case of a patient with a solitary fibrous tumor of kidney with malignant findings with distant metastasis and nephrectomy managed with subcutaneous interferon achieving 23 months of progression-free survival. To date there is no prospective evaluation of any specific modality of treatment, but the surgical management and long-term followup are the only ones so far recommended strategies in the management of these patients. Studies are awaited with more patients to evaluate the different strategies of systemic therapy reported so far to allow adding survival benefit.

Hiponatremia luego de uso de cisplatino: a propósito de un caso / Hyponatraemia after cisplatin use: a case report

Paciente de 26 años con diagnóstico de teratoma inmaduro de ovario derecho. Se le realizó resección del tumor más salpingooforectomía en junio de 2014. Recibió manejo adyuvante con carboplatino y ciclofosfamida por un ciclo en enero de 2015, pero sin respuesta. Se realizó laparotomía exploradora por obstrucción intestinal evidenciándose masa pélvica e implantes peritoneales a nivel hepático. Valoró oncología clínica del INC en febrero del 2015, se inicia manejo con esquema PEB; recibió el primer ciclo sin complicaciones. El segundo ciclo fue retrasado por infección en la pared abdominal. Empezó tratamiento con sodio sérico normal, con posterior descenso sin alteración en el resto de electrolitos, función renal, ni estado ácido base. La paciente no presentó síntomas neurológicos y estuvo euvolémica. Se inició estudio de hiponatremia haciéndose diagnóstico de SIADH. Se indicó manejo con restricción hídrica y dieta hipersódica, con posterior ascenso gradual de niveles séricos de Na, considerándose SIADH secundario a uso de cisplatino.

The case is presented of a 26 year-old patient diagnosed with an immature teratoma of the right ovary. Tumour resection plus salpingo-oophorectomy was performed in June 2014. She received one cycle of adjuvant treatment with carboplatin and cyclophosphamide, but with no response. An exploratory laparotomy was performed due to an intestinal obstruction, which showed a pelvic mass and peritoneal implants at hepatic level. She was assessed in the oncology clinic of the Colombian National Institute (INC) in February 2015, and treatment with a platinol (cisplatin), etoposide, and bleomycin (PEB) scheme was started. She received the first cycle without complications, but the second cycle was delayed due to an infection in the abdominal wall. She started the treatment with a normal serum sodium, with a subsequent decrease with no changes in the rest of the electrolytes, kidney function, or acid-base status. The patient showed no neurological signs and was euvolaemic. A hyponatraemia study was performed, ending up making the diagnosis of inappropriate antidiuretic hormone secretion (IADHS). A water restriction and high sodium diet was indicated, with the subsequent gradual increase in the serum Na levels. The IADHS was considered secondary to the use of cisplatin.