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Purpose: To describe the clinical course and evaluate treatment of ocular surface changes in patients receiving immune checkpoint inhibitor (ICI) therapy., Methods: Multiple markers of ocular surface dryness were evaluated in 16 patients on ICI therapy. The Wilcoxon rank-sum test was used to determine the significant change in the initial and final ocular surface indices., Results: Fifty percent of the eyes demonstrated worsening Schirmer I scores; 29% showed an increase in lissamine green staining. During follow-up, 43% of patients experienced a decline in OSDI scores. Treatments included preservative-free artificial tears (88%), cyclosporine (25%), topical corticosteroids (31%), warm compresses (25%); punctal plugs (13%). Median follow-up time was 3.4 months (range:0-79 ); median ICI treatment duration was 7 months (range:1-40). Four patients died during the observation period., Conclusion: A significant proportion of patients experience changes in ocular surface markers while treated with ICIs. Medical intervention can lead to stabilization of ocular surface disease.

The incidence of melanoma has been dramatically increasing over the last decades. Melanoma is considered to have a high metastatic potential and it can progress via lymphatic vessels or through hematogenous metastasis. Different patterns of recurrence have been described, namely, local, satellite, and in transit metastasis (LCIT), lymphatic metastasis, and systemic metastasis. With a more advanced melanoma stage at diagnosis, there is a higher risk for systemic metastasis in comparison to LCIT; in contrast, early-stage melanoma tends to recur more frequently as LCIT and less commonly as systematic metastasis. The aim of this review was to summarize the patterns of recurrence of cuta-neous melanoma, giving the clinician a practical summary for diagnosis, prognosis, and surveillance. There is a knowledge gap of the common patterns of recurrence that needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies as well as patient counseling.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% ( p = 0.338), whereas NAb positivity reached 100% and 92% ( p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Objectives: Perioperative and adjuvant chemotherapy have demonstrated clinical benefits in localized gastric cancer. Nevertheless, the reports on their effects on patient's health-related quality of life (HRQoL) are scarce. Here, we prospectively assessed quality of life and the incidence of chemotherapy-induced peripheral neuropathy (CIPN) in a cohort of patients treated with adjuvant FOLFOX., Methods: Localized stomach or gastroesophageal junction adenocarcinoma patients who underwent curative resection were recruited at a single center. All patients received adjuvant FOLFOX6, and HRQoL and CIPN were assessed using the European organization for research and treatment of cancer quality life (EORTC) C30 and the EORTC CIPN20 questionnaires, respectively. Clinically significant deterioration of HRQoL was also assessed as a coprimary outcome in a longitudinal analysis., Results: We recruited a total of 63 patients. Median age was 62.5 years, and 75% had stomach tumors. Twenty-four weeks after the start of treatment, the probability of being free from HRQoL deterioration and CIPN was 29% (95% confidence interval [CI] 18%-42%) and 6% (95% CI 2%-17%), respectively. Five-year disease-free survival was 45% (95% CI 24%-64%) and 5-year overall survival was 63% (95% CI 48%-76%)., Conclusions: Adjuvant FOLFOX is associated with a high rate of long-term survival in localized gastric cancer; nevertheless, it has detrimental effects on patients' quality of life., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine., Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses., Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P  = 0.035) and NAb positivity (77.4% vs 55.1%, P  = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups., Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster., Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509., Competing Interests: S.M.B., N.L.C. and A.K. reported having participated as leading scientists for design of CoronaVac clinical trials sponsored in Chile by Pontificia Universidad Católica de Chile and in collaboration with Sinovac Biotech (NCT04651790 and NCT04992260)., (© 2022 The Author(s).)

Few studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients., Methods: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined., Results: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups., Conclusions: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients., Clinical Trials Registration: NCT04888793., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In Chile, colorectal cancer ranks third in incidence and fifth in mortality. Half of these patients have liver metastases at the diagnosis, and only 30% of them are resectable. Despite the development of many complex hepatobiliary procedures to achieve the total resection of metastases, the long-term survival with these techniques is not good. Liver transplantation is an alternative to treat unresectable liver metastasis from colorectal cancer with a good outcome. Several prognostic scores allow the selection of patients with good tumor biology. These patients have better overall and disease-free survival after liver transplantation. The use of immunosuppressive treatment doesn't increase recurrence, and even the pattern of tumor growth is slower in liver transplant recipients. The purpose of this review is to summarize the current evidence in this topic and to highlight the need for a formal protocol for liver transplantation for unresectable colorectal liver metastases, using living donors or marginal grafts to avoid competition with the rest of the national waiting list.

Background: While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours., Methods: Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020., Results: In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS)., Conclusions: A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC)., Methods: Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided., Results: In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P < .001 for both comparisons), rectal bleeding (35 years and younger = 41.1%; 36-49 years = 41.0%; AO = 25.9%; P = .001 and P < .001, respectively), and abdominal pain (35 years and younger = 37.1%; 36-49 years = 34.0%; AO = 26.8%; P = .01 and P = .005, respectively) were more common in EO-CRC. Among microsatellite stable tumors, we found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and Receptor Tyrosine Kinase signaling pathway (RTK-RAS)alterations were noted by age. However, on multivariate analysis including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated. Among advanced microsatellite stable CRCs, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients 35 years and younger vs 14.1% of AO-CRC (P = .01)., Conclusions: EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited., Materials and Methods: Patients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response., Results: ctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%-99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%-74%) were concordant with plasma ctDNA. ctDNA matched patients to ALK-directed therapy with subsequent clinical response, including four patients matched on the basis of ctDNA results alone due to inadequate or delayed tissue testing. Serial ctDNA analysis detected MET amplification (n = 2) and ALK G1202R mutation (n = 2) as mechanisms of acquired resistance to ALK-directed therapy., Conclusion: Our findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Thymic epithelial tumours are rare and highly heterogeneous. Reports from the United States suggest an overall incidence of 0.15 per 100,000/year. In contrast, the incidence of these tumours in Latin America is largely unknown and reports are scarce, somewhat limited to case reports., Methods: Herein, we report a series of 38 thymic tumours from a single institution, retrospectively incorporated into this study. Patient characteristics and outcomes including age, sex, stage, paraneoplastic syndromes, treatment regimens and the date of decease were obtained from medical records., Results: Most cases in our series were females and young age (<50 years old) and early stage by Masaoka-Koga or the Moran staging systems. Also, a 34% of patients had myasthenia gravis (MG). Next, we analysed overall survival rates in our series and found that the quality of surgery (R0, R1 or R2), MG status and staging (Masaoka-Koga, Moran or TNM) were prognostic factors. Finally, we compared our data to larger thymic tumour series., Conclusions: Overall, our study confirms complete surgical resection as the standard, most effective treatment for thymic epithelial tumours. Also, the Masaoka-Koga staging system remains as a reliable prognostic factor but also the Moran staging system should be considered for thymomas., (© the authors; licensee ecancermedicalscience.)

Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression., Methods and Findings: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion., Conclusions: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration., Trial Registration: NCT04375098., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: -S.M. is a consultant for Foundation Medicine and Roche; he also has received research funding from Bristol-Myers Squibb and Foundation Medicine. - C.C is the Head of Cancer Research Department at Instituto Oncológico Fundación Arturo López Pérez (FALP) and declares that FALP has received funding from "Confederación de la producción y el Comercio (CPC)" to develop research based on Convalescent Plasma from COVID-19 recovered patients to treat patients with active COVID-19 infection. None of the authors from FALP has received any payment for their participation in this publication nor for participating in the trial in their investigator roles.

Background: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain., Materials and Methods: We retrieved and analysed medical records from a total of 156 Chilean stage I-III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres., Results: Median age was 51 years (range: 24-81); 13.5% ( n = 21) received Cb-containing regimens, 80.1% ( n = 125) received sequential anthracyclines plus taxanes; 29.5% ( n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% ( n = 8) for the Cb-containing group ( p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216)., Conclusions: To the best of authors' knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors' results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment., (© the authors; licensee ecancermedicalscience.)

Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein-Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53-). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic.

Objective: Clinical guidelines recommend the use of endocrine therapy (ET) in advanced hormone receptor positive (HR+) human epidermal growth factor receptor type 2 negative (HER2-) breast cancer (BC) patients in the absence of visceral disease or ET resistance. Furthermore, studies indicate similar response and survival rates using ET or cytotoxic chemotherapy (CT). Methods: Herein, we assessed clinical characteristics, type of systemic therapy and survival rates of advanced HR + HER2-BC patients in our database. Results: A total of 172 advanced HR + HER2-BC patients were treated at our institution between 1997 and 2019. Sixty percent received first-line ET (4% received combined ET). Median age of this subset was 55 years (range: 30-86). Similarly, the median age of patients that received CT was 54 years (range: 21-83). Over time, 30% of patients received ET in the 2000-2005 period; this increased to 70% in the 2016-2019 period ( p  = .045). Overall survival (OS) was 97 months and 51 months for patients treated with ET or CT, respectively ( p  = .002). Conclusions: To the best of our knowledge this is the first study assessing the use of ET in Chilean advanced HR + HER2-BC patients. Several patients in our institution receive CT without indication. The increase in ET usage over time can be attributed to better and faster immunohistochemical detection methods for Estrogen Receptor (ER), changes in educational and government policies, and a wider variety of ET options. Finally, clinical trials have failed to demonstrate a substantial benefit of CT over ET in this setting.

Purpose: Like other malignancies, GI stromal tumors (GIST) are highly heterogeneous. This not only applies to histologic features and malignant potential, but also to geographic incidence rates. Several studies have reported GIST incidence and prevalence in Europe and North America. In contrast, GIST incidence rates in South America are largely unknown, and only a few studies have reported GIST prevalence in Latin America., Patients and Methods: Our study was part of a collaborative effort between Chile and Mexico, called Salud con Datos. We sought to determine GIST prevalence and patients' clinical characteristics, including survival rates, through retrospective analysis., Results: Overall, 624 patients were included in our study. Our results found significant differences between Mexican and Chilean registries, such as stage at diagnosis, primary tumor location, CD117-positive immunohistochemistry status, mitotic index, and tumor size. Overall survival (OS) times for Chilean and Mexican patients with GIST were 134 and 156 months, respectively. No statistically significant differences in OS were detected by sex, age, stage at diagnosis, or recurrence status in both cohorts. As expected, patients categorized as being at high risk of recurrence displayed a trend toward poorer progression-free survival in both registries., Conclusion: To the best of our knowledge, this is the largest report from Latin America assessing the prevalence, clinical characteristics, postsurgery risk of recurrence, and outcomes of patients with GIST. Our data confirm surgery as the standard treatment of localized disease and confirm a poorer prognosis in patients with regional or distant disease. Finally, observed differences between registries could be a result of registration bias.

Purpose: While mutations in BRAF in metastatic colorectal cancer (mCRC) most commonly occur at the V600 amino acid, with the advent of next-generation sequencing, non-V600 BRAF mutations are increasingly identified in clinical practice. It is unclear whether these mutants, like BRAF V600E, confer resistance to anti-EGFR therapy., Experimental Design: We conducted a multicenter pooled analysis of consecutive patients with non-V600 BRAF-mutated mCRCs identified between 2010 and 2017. Non-V600 BRAF mutations were divided into functional classes based on signaling mechanism and kinase activity: activating and RAS-independent (class 2) or kinase-impaired and RAS-dependent (class 3)., Results: Forty patients with oncogenic non-V600 BRAF-mutant mCRC received anti-EGFR antibody treatment [ n = 12 (30%) class 2 and n = 28 (70%) class 3]. No significant differences in clinical characteristics were observed by mutation class. In contrast, while only 1 of 12 patients with class 2 BRAF mCRC responded, 14 of 28 patients with class 3 BRAF responded to anti-EGFR therapy (response rate, 8% and 50%, respectively, P = 0.02). Specifically, in first- or second-line, 1 of 6 (17%) patients with class 2 and 7 of 9 (78%) patients with class 3 BRAF mutants responded ( P = 0.04). In third- or later-line, none of 6 patients with class 2 and 7 of 19 (37%) patients with class 3 BRAF mutants responded ( P = 0.14)., Conclusions: Response to EGFR antibody treatment in mCRCs with class 2 BRAF mutants is rare, while a large portion of CRCs with class 3 BRAF mutants respond. Patients with colorectal cancer with class 3 BRAF mutations should be considered for anti-EGFR antibody treatment. See related commentary by Fontana and Valeri, p. 6896 ., (©2019 American Association for Cancer Research.)

Background: Plasma cfDNA evaluation at acquired resistance to targeted therapies in lung cancer is routine, however, reports of extended clinical application and pitfalls in laboratory practice are still limited. In this study we describe our experience with cfDNA testing using EGFR T790M as a prototype. Methods: Patients with metastatic EGFR -mutant NSCLC patients who underwent plasma EGFR T790M testing at acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) from January 2016 through August 2017 were identified. Molecular laboratory records were reviewed to assess performance of testing by digital PCR, concordance between plasma and tissue testing, turnaround time (TAT), plasma T790M variant allele frequency (VAF), and its correlations with metastatic sites and clinical outcomes. Results: 177 patients underwent T790M cfDNA testing during this period. Plasma T790M was positive in 32% of patients. The median TAT was shorter for plasma T790M compared to tissue PCR (9 vs. 15 days, p  < .0001), and led to osimertinib use in 84% of positive patients. In 52 patients with plasma and tissue T790M evaluation, the concordance was 77%. Plasma T790M VAF did not correlate with time to osimertinib discontinuation ( p  = .4). Plasma T790M status correlated with a higher number of metastatic sites (4 vs. 3, p  < .001) and bone metastases ( p  = .0002). Conclusion: Plasma EGFR T790M testing had shorter TAT compared to tissue testing, however, it was longer than anticipated. Test sensitivity is higher in patients with osseous metastases and with higher metastatic burden suggesting a more limited role for early detection. T790M VAF was not associated with clinical outcomes.

Rectal cancer accounts for one-third of newly diagnosed colorectal cancer cases. Given its anatomical location and risk for local recurrence, a multidisciplinary treatment program including surgery, radiation therapy, and chemotherapy has demonstrated improved outcomes in localized disease. Genetic analysis has become part of the standard approach for management of advanced disease and new trials are considering tailored therapies for locally advanced disease. This review describes molecular subsets of colorectal cancer; implications for clinical management, including patterns of metastatic spread and response to therapies; and emerging matched therapies. During the last decade, significant biological differences have been noted based on colorectal cancer primary location and here we focus on rectal cancers and relevant markers for this disease. As more treatment for localized rectal cancer is shifted to the neoadjuvant setting and more targeted regimens are developed for metastatic disease, radiologists will increasingly see patients defined by molecular subsets and their awareness of the genetics of rectal cancer will help further refine our understanding of this disease.

Purpose: Biliary tract cancers (BTCs), which include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (EHC), and gallbladder cancer (GBC), have limited treatment options. We sought to comprehensively examine the clinical and molecular characteristics of BTCs with amplification or mutation of ERBB2 ., Methods: Demographic, outcome, and treatment response data were collected for patients with ERBB2 -altered BTC identified by next-generation sequencing with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets from 2014 to 2018., Results: A total of 517 patients with BTC underwent next-generation sequencing (ICC, n = 313; EHC, n = 93; GBC, n = 111). Twenty-eight patients (5.4%) had ERBB2 alterations, including 2.7% with ERBB2 gene amplification, 2.3% with ERBB2 mutation, and 0.4% with concurrent amplification and mutation. The prevalence of ERBB2 gene alterations was significantly higher in GBC (12.6%) than in ICC (2.2%) and EHC (7.5%; P < .001). In ERBB2- amplified tumors, the median fold change was 6.4 (range, 2.1 to 19.7), while in ERBB2 -mutant tumors, the most frequent mutated domain was the extracellular domain (32%), with all mutations in this region involving the S310 codon. Frequent co-altered genes in this cohort were TP53 (54%), PIK3CA (21%), and CDKN2A (18%); KRAS amplification/mutation was found in 7% of patients. One patient with ERBB2 -amplified EHC who enrolled in a basket trial (ClinicalTrials.gov identifier: NCT02675829) had a partial response to the human epidermal growth factor receptor 2-targeted antibody-drug conjugate ado-trastuzumab emtansine., Conclusion: ERBB2 alterations are present in 5.4% of BTCs. When present, the degree of ERBB2 gene amplification is often high, and S310 codon mutations are the most common hotspot. These features, along with the presented case, support further development of human epidermal growth factor receptor 2-targeted therapy in ERBB2 -mutant and/or -amplified BTC., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Sebastian MondacaConsulting or Advisory Role: Foundation MedicinePedram RazaviConsulting or Advisory Role: Novartis Research Funding: GRAIL (Inst), Illumina (Inst)Chongrui XuHonoraria: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche Consulting or Advisory Role: Boehringer Ingelheim, Pfizer Travel, Accommodations, Expenses: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Pfizer, Roche, Bristol-Myers Squibb, MSDMichael OffinConsulting or Advisory Role: PharmaMar, Novartis, Targeted Oncology Travel, Accommodations, Expenses: Bristol-Myers Squibb, Merck Sharp & DohmeMaurizio ScaltritiStock and Other Ownership Interests: Loxo Oncology Honoraria: Menarini, ADC Therapeutics Consulting or Advisory Role: Menarini Research Funding: Menarini (Inst), Immunomedics (Inst), TargImmune Therapeutics (Inst), Puma Biotechnology (Inst), Daiichi Sankyo (Inst) Patents, Royalties, Other Intellectual Property: “PI3K Inhibitors and Uses Thereof,” US Provisional Application No. 62/742,163, inventors: Maurizio Scaltriti, Dan Heller, José Baselga, Yosef Shamay, Carles Monterrubio, Amaia Arruabarrena (Inst); “Methods for Detecting HER2 Dimerization in Patients With HER2 Mutant Lung Cancers and Predicting Responsiveness to Ado-Trastuzumab Emtansine Therapy,” SK2018-038-01, inventors: Maurizio Scaltriti, Bob T. Li (Inst); “Methods for Predicting Responsiveness of Lung Cancer Patients to HER2-Targeting Therapies,” US Provisional Application No. 62/685,057, inventors: Maurizio Scaltriti, Bob T. Li (Inst) Travel, Accommodations, Expenses: MenariniJaclyn F. HechtmanHonoraria: WebMD Consulting or Advisory Role: COR2ED, Axiom Healthcare Strategies Research Funding: Bayer AG, Eli Lilly, Boehringer IngelheimEileen M. O’ReillyConsulting or Advisory Role: Ipsen, Merck Research Funding: AstraZeneca (Inst), MedImmune (Inst)Michael F. BergerConsulting or Advisory Role: Roche Research Funding: GRAILDavid B. SolitStock and Other Ownership Interests: Loxo Oncology Consulting or Advisory Role: Pfizer, Loxo Oncology, Illumina, Intezyne Technologies, Vivideon Therapeutics, Eli Lilly Travel, Accommodations, Expenses: Merck KGaABob T. LiConsulting or Advisory Role: Roche, Biosceptre International, Thermo Fisher Scientific, Mersana, Guardant Health, Hengrui Therapeutics Research Funding: Roche (Inst), Genentech (Inst), Illumina (Inst), BioMed Valley Discoveries (Inst), AstraZeneca (Inst), GRAIL (Inst), Daiichi Sankyo (Inst), Hengrui Therapeutics (Inst), Guardant Health (Inst), Amgen (Inst)Ghassan K. Abou-AlfaConsulting or Advisory Role: Astellas Pharma, Celsion, Celgene, Sanofi, Silenseed (I), Sillajen, Boston Scientific, CASI Pharmaceuticals, Onxeo, Roche, Bristol-Myers Squibb, EMD Serono (I), Gilead Sciences (I), Vicus Therapeutics (I), Servier, Agios, Aslan Pharmaceuticals, Bayer AG, Delcath Systems, Eisai, Halozyme, Ipsen, Merck Serono, Sirtex Medical, AstraZeneca, MedImmune, Amgen, Antengene, Aptus Clinical, Carsgen Therapeutics, CytomX Therapeutics (I), Daiichi Sankyo, Debiopharm Group, Exelixis, Inovio Pharmaceuticals, PCI Biotech, Yakult, 3DMedcare, Alignmed, BeiGene, BiolineRx, BridgeBioPharma, Cipla, Genoscience Pharma, Hengrui Pharmaceutical, Jazz Pharmaceuticals, Kyowa Hakko Kirin, Janssen Pharmaceuticals (I), LAM Therapeutics, Eli Lilly, Loxo Oncology (I), Mina, Newlink Genetics (I), Novella Clinical, Pfizer (I), Pharmacyte Biotech (I), Pharmacyclics (I), Pieris Pharmaceuticals (I), QED, RedHill Biopharma, SOBI (I), Targovax (I), Tekmira, twoXAR, Yiviva Research Funding: Bayer AG (Inst), Exelixis (Inst), Genentech (Inst), Roche (Inst), CASI Pharmaceuticals (Inst), MedImmune (Inst), AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Incyte (Inst), MabVax (Inst), Momenta Pharmaceuticals (Inst), OncoMed (Inst), Agios (Inst), Array BioPharma (Inst), Celgene (Inst), Eli Lilly (Inst), Novartis (Inst), Acta Biologica (Inst), BeiGene (Inst), Halozyme (Inst), Polaris (Inst), OncoQuest (Inst), Puma Biotechnology (Inst), QED (Inst) Travel, Accommodations, Expenses: Polaris No other potential conflicts of interest were reported., (© 2019 by American Society of Clinical Oncology.)

Locally advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma are associated with a grim prognosis. The development of highly effective systemic therapies for these tumors has been challenging; however, numerous locoregional treatment alternatives have emerged, including transarterial hepatic embolization (TAE), transarterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), hepatic arterial infusion chemotherapy (HAI), radioembolization, and stereotactic body radiation therapy. Although there is potential for long-term disease control for these therapies, the evidence to guide adequate patient selection and choose among different treatment alternatives is still limited. This review focuses on the rationale and data supporting TAE, TACE, DEB-TACE, and HAI in hepatobiliary cancers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53 , NRAS , and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

Biliary tract cancer (BTC) is comprised of intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (EHC) and gallbladder cancer (GBC). These tumors arise in the biliary epithelium, share histological characteristics and are associated with grim prognosis even when diagnosed at early stages. Moreover, its relatively low incidence in developed countries has precluded the development of clinical trials addressing specific differences among BTC subgroups in terms of their biology, treatment response and clinical outcomes. In this scenario, the development of effective treatment strategies for patients has been rather modest. To date, the combination of cisplatin plus gemcitabine remains as the standard first line therapy in advanced disease and after progression to this regimen there are limited treatment options. Next generation sequencing (NGS) studies have assessed the distribution of driver genes and potentially actionable genomic alterations among ICC, EHC and GBC. Here, we outline genomic differences among these subsets and describe key milestones in order to develop novel targeted drugs against BTCs. Although the early results of several studies are promising, international collaboration is critical to conduct adequately-powered trials, enrolling patients from high-incidence countries.

Background: Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC., Patients and Methods: We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy - essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin - in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers., Results: Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations., Conclusions: FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial., Methods: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity., Results: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia., Conclusion: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411.

Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.

Purpose: Increasing numbers of reports have shown acceptable short-term mortality of patients with cancer admitted into the intensive care unit (ICU). The aim of this study was to determine the mortality of critically ill patients with cancer admitted to the ICU in a general hospital in Chile., Materials and Methods: This was a prospective cohort trial in which we included all patients with cancer admitted to the ICU between July 2015 and September 2016. Demographic, physiologic, and treatment data were registered, and survival at 30 days and 6 months was evaluated. A prespecified subgroup analysis considering the admission policy was performed. These subgroups were (1) ICU admission for full code management and (2) ICU trial (IT)., Results: During the study period, 109 patients with cancer were included. Seventy-nine patients were considered in the full code management group and 30 in the IT. The mean age of patients was 60 years (standard deviation [SD], 15), and 56% were male. Lymphoma was the most frequent malignancy (17%), and 59% had not received cancer treatment because of a recent diagnosis. The mean Acute Physiology and Chronic Health Evaluation and Sequential-Related Organ Failure Assessment scores were 22.2 (SD, 7.3) and 7 (SD, 3), respectively. There were no differences in vasopressor, fluid, or transfusion requirements between subgroups. Lactate levels, Sequential-Related Organ Failure Assessment scores (day 1, 3, and 5), complications, and ICU length of stay were similar. In the entire cohort, 30-day and 6-month mortality was 47% and 66%, respectively. There was no difference in mortality between subgroups according to the admission policy., Conclusion: Patients admitted to the ICU in a developing country are at high risk for short-term mortality. However, there is a relevant subgroup that achieves 6-month survival, even among patients who undergo an IT.

Background: Regorafenib is a therapeutic alternative for patients with metastatic colorectal cancer (MCRC) resistant to conventional therapies. The reported toxicity is relevant and there is no data on Latin American patients. The objective was to evaluate the overall survival (OS), progression-free survival (PFS) and quality of life (QoL) in a prospective cohort of Latin American patients treated with an adjusted dose of regorafenib., Methods: We prospectively recruited patients with MCRC that progressed to standard therapy. A dose escalation algorithm was used. OS, PFS, response rate and QoL were evaluated., Results: We recruited 13 patients between June and November 2015. The median age was 60 years. Median OS was 8.6 months and median PFS was 2.2 months. The response rate was 8%. Grade 3-4 toxicities included grade 3 palmoplantar erythrodysesthesia in 23% and grade 3 fatigue in 12% of patients., Conclusion: Regorafenib treatment is effective in Latin American patients with conventional therapy resistant MCRC.

The widespread use of next generation sequencing (NGS) has led to a refined understanding of the genomics of colorectal cancer (CRC). However, progress in the use of molecular biomarkers in standard practice has been slow, and there is no approved targeted therapy for CRC based on a positive predictive marker yet. In this review, we will first summarize biomarkers with clinical utility in standard practice or targeted therapy trials and then consider how to rationally design clinical trials to more effectively target CRC. Specifically, we will discuss current clinical applications of genomic information consisting of the use of the MAPK (mitogen-activated protein kinase) pathway genes KRAS , NRAS , and BRAF as prognostic and predictive biomarkers for standard treatment, risk stratification by primary tumor site and consideration of tumor laterality in patient selection for epidermal growth factor receptor (EGFR) antibody treatment, and the evaluation for genomic biomarkers, including BRAF V600E, HER2 amplification, and gene rearrangements, for targeted therapies in clinical trials. Applying lessons from targeted therapy trials in CRC, we now appreciate that both tumor genomics and tissue of origin affect targeted therapy response and that the development of resistance to targeted therapies is dynamic and often subclonal. Based on these understandings, we propose the design of adaptive clinical trials that evaluate real-time pharmacodynamic markers and monitor tumor subpopulations during the course of treatment to overcome challenges targeting genetic drivers in CRC., Competing Interests: Conflicts of Interest: R Yaeger has served on an advisory board for GlaxoSmithKline. S Mondaca has no conflicts of interest to declare.

Gastric cancer (GC) is the world's second-leading cause of neoplastic mortality. Genetic alterations, response to treatments, and mortality rates are highly heterogeneous across different regions. Within Latin America, GC is the leading cause of cancer death in Chile, affecting 17.6 per 100,000 people and causing >3000 deaths/y. Clinical outcomes and response to "one size fits all" therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response.The Gastric Cancer Task Force is a Chilean collaborative, noninterventional study that seeks to stratify gastric adenocarcinomas using clinical outcomes and genomic, epigenomic, and protein alterations in a cohort of 200 patients. Tumor samples from the Pathology Department and the Cancer Center at UC-Christus healthcare network, Pontificia Universidad Católica de Chile will be analyzed using a panel of 143 known cancer genes (Oncomine Comprehensive Assay) at the Center of Excellence in Precision Medicine in Santiago, Chile. In addition, promoter methylation for selected genes will be performed along with tissue microarray for clinically relevant proteins (e.g., PD-L1, Erb-2, VEGFR2, among others) and Helicobacter pylori and Epstein-Barr virus status. Obtained data will be correlated to 120 clinical parameters retrieve from medical records, including general patient information, cancer history, laboratory studies, comorbidity index, chemotherapy, targeted therapies, efficacy, and follow-up.The development of a clinically meaningful classification that encompasses comprehensive clinical and molecular parameters may improve patient treatment, predict clinical outcomes, aid patient selection/stratification for clinical trials and may offer insights into future preventive and/or therapeutic strategies in patients from Latin America region., Trial Registration: ClinicalTrials.gov Identifier: NCT03158571, Registered on May 18, 2017.

Introduction: Involvement of the central nervous system (CNS) secondary to colorectal cancer is infrequent and associated with a poor prognosis. Its treatment is extrapolated from metastases of other origins as the information available on this scenario is limited. The goal of this study is to assess the clinical characteristics of a series of patients and determine the results in terms of progression-free survival (PFS) and global survival., Method: The records of patients with CNS metastasis of colorectal origin who were treated in this facility between the years 2001 and 2016 were reviewed retrospectively., Results: 20 patients with CNS lesions of this origin were identified. Of these, 45% were male and 55% were female (average age 65.5 years). The histology corresponded to tubular adenocarcinoma in 95% of cases. Around 85% of the patients showed a neurological deficit, and their recursive partitioning analysis (RPA) classifications were 1 in 20%, 2 in 55%, and 3 in 25% of the cases studied. The treatments provided were: holocerebral radiotherapy (45%), stereotactic radiosurgery (25%), surgery followed by holocerebral radiotherapy (25%), and exclusively palliative care (5%). The PFS was 2.6 months from treatment of the CNS lesion, while the median survival was 3.8 months. The survival times for patients receiving different treatments were as follows: surgery plus holocerebral radiotherapy 16.2 months, stereotactic radiotherapy 12 months, and holocerebral radiotherapy 2.4 months (p = 0.003)., Conclusion: The prognosis for patients with metastasis of colorectal origin is poor. The patients treated with surgery or stereotactic radiotherapy can have a greater survival.

Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III., Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates., Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used., Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94)., Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.