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Cancer genetic counseling in Chile: Addressing barriers, confronting challenges, and seizing opportunities in an underserved Latin American Community
No full textPurpose: Despite the rapid advancements in genomics and the enactment of a new cancer law in Chile, the implementation of cancer genetic counseling continues to face significant challenges because of limited resources and infrastructure. Methods: We conducted a survey targeting health care providers who offer genetic counseling to patients with cancer and possess training in genetics and counseling. Additionally, we distributed a separate survey to high-risk patients associated with an advocacy group to gather insights on their perceptions of and experiences with cancer genetic counseling. Results: Among the surveyed providers, 21% were nonmedical professionals who developed their skills through postgraduate continuing education programs. Germline testing was not performed in 47% of cases. Among the participants, 37% considered genetic counseling important for understanding the cause of their cancer, 25% valued knowing their risk of developing future tumors, and 33% believed it would benefit their current cancer treatment. Just over half of the patients (54%) had access to genetic counseling. Among those that received genetic counseling, 85% found it beneficial. Conclusion: In Chile, barriers to genetic counseling persist, particularly in rural areas and because of a shortage of trained professionals. Public policies recognizing genetic counseling's importance are crucial, along with expanding training and infrastructure. Understanding patient perceptions and increasing the number of trained genetic counseling into cancer care, educating clinicians, and advocating for increased access are key steps for enhancing cancer treatment effectiveness in Chile. © 2024 The Author
Preventing and Treating Pain and Anxiety during Needle-Based Procedures in Children with Cancer in Low- and Middle-Income Countries
No full textIntroduction: Children with cancer experience significant pain and anxiety during needle-based procedures. Undertreated pain in children has long-lasting consequences and reduces the efficacy of subsequent analgesic efforts. A validated quality improvement (QI) intervention, known as the “Children’s Comfort Promise”, includes (1) topical anesthetics, (2) sucrose or breastfeeding for infants, (3) comfort positioning, and (4) distraction techniques, and has been shown to be highly effective in decreasing procedural pain and anxiety in children. However, there is limited data about the adoption, adaptation, and implementation of these interventions in low- and middle-income countries (LMICs). Methods: A QI pilot project utilizing the Model for Improvement of the “Global Comfort Promise” was implemented in four global pediatric cancer hospitals (Lima, Peru; Barretos, Brazil; Pietermaritzburg, South Africa; and Manila, Philippines). Between August 2021 and January 2023, the pilot sites identified a specific aim, co-designed the measurement strategy with St. Jude Children’s Research Hospital, and adopted, adapted, and implemented the project at their individual sites. Results: A total of 2,185 different procedures were recorded in the first year of implementation. Most patients were less than 10 years old (60.5%) and solid tumors (37.9%) were the most common diagnosis. Overall, healthcare professionals (98.3%) were satisfied with the procedures. Parents and patients reported that only 33.7% of patients experienced pain during the procedure. All (100%) parents and patients felt the healthcare teams adequately addressed their child’s pain. Median self-reported adherence to ≥2 interventions was 98.0%. Challenges to the implementation of the QI initiative included lack of training, turnover of the medical staff, maintaining staff enthusiasm, and access to topical anesthetics. Each site had unique change ideas to implement the initiative. Conclusions: This multi-site, multi-country QI initiative was feasible and was successfully adopted, adapted, and implemented in the LMIC context to improve procedural pain in children (Global Comfort Promise). Additionally, this intervention resulted in high satisfaction of both healthcare professionals and patients/families. Further work is needed to overcome the challenges of topical anesthetic access and education of the workforce. Additional plans include modifying the Global Comfort Promise to include high-quality communication and expanding to additional sites with further refinement of the implementation strategy. © 2024 by the authors
Ethnic inequalities in coverage and use of women’s cancer screening in Peru
No full textObjective: This study aimed to assess ethnic inequalities in the coverage and utilization of cancer screening services among women in Peru. Methods: Data from the 2017–2023 Demographic and Family Health Survey in Peru were analyzed to evaluate ethnic disparities in screening coverage for breast and cervical cancer, including clinical breast examination (CBE), Pap smear test (PST), and mammography. Measures such as the GINI coefficient and Slope Index of Inequality (SII) were used to quantify coverage and utilization disparities among ethnic groups. Results: The study included 70,454 women aged 30–69. Among women aged 40–69, 48.31% underwent CBE, 84.06% received PST, and 41.69% underwent mammography. It was found inequalities in coverage for any cancer screening (GINI: 0.10), mammography (GINI: 0.21), CBE (GINI: 0.19), and PST (GINI: 0.06), in 25 Peruvian regions. These inequalities were more pronounced in regions with larger populations of Quechua, Aymara, and Afro-Peruvian women. In rural areas, Quechua or Aymara women (SII: -0.83, -0.95, and − 0.69, respectively) and Afro-Peruvian women (SII: -0.80, -0.92, and − 0.58, respectively) experienced heightened inequalities in the uptake of CBE, mammography, and PST, respectively. Like Quechua or Aymara women (SII: -0.50, SII: -0.52, and SII: -0.50, respectively) and Afro-Peruvian women (SII: -0.50, SII: -0.58, and SII: -0.44, respectively) with only a primary education. Conclusion: Ethnic inequalities affect breast and cervical cancer screening coverage across regions in Peru. In Quechua, Aymara, and Afro-Peruvian women the uptake of mammography, CBE, and PST was less frequently than their white or mestizo counterparts. These inequalities are attributed to sociodemographic conditions such as lower education levels and residence in rural or non-capital areas
Exploring treatment decision-making at diagnosis for children with advanced cancer in low- and middle-income countries
No full textPurpose: Global childhood cancer survival outcomes correlate with regional contextual factors, yet upfront treatment decision-making for children with advanced or poor prognosis cancer in low- and middle-income countries (LMICs) is not well understood. This study aimed to (1) characterize the landscape of contextual factors that shape physician decision-making at diagnosis for these children in LMICs and (2) describe physician rationales for if/when to offer treatment with non-curative intent, including how they define “poor prognosis” during treatment decision-making. Methods: An international panel of pediatric oncologists practicing in LMICs participated in two focus groups structured for the collaborative generation of factors influencing treatment decision-making, including consideration of non-curative treatment pathways at diagnosis. Thematic analysis of qualitative data was conducted, followed by member checking. Results: Eleven pediatric oncologists participated, representing all global regions defined by the World Health Organization. Participants identified a broad range of factors influencing decision-making across multiple levels, including the individual, hospital, health system, community, and country levels. All participants agreed that treatment with non-curative intent could be offered at diagnosis in certain contexts, and diverse definitions for poor prognosis were described. Conclusions: Upfront treatment decision-making for children with advanced or poor prognosis cancer in LMICs is variable and challenging. Difficulties with decision-making in LMICs may be amplified by inconsistent definitions of poor prognosis and underrepresentation of the factors that influence treatment decision-making within existing decision-making frameworks or childhood cancer treatment guidelines. Future research should explore decision-making approaches, preferences, and challenges in depth from the perspectives of pediatric cancer patients, families, and multidisciplinary clinicians. © The Author(s) 2024
NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
No full textDespite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell–directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates antitumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of natural killer (NK) cells in an IFNγ-dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-programmed death (PD) L1 therapy and increased NK:T-cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK-cell function. Combining anti-NKG2A and anti–PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tumor-infiltrating NK and CD8+ T cells. These results suggest that similar strategies may enhance patient benefit in clinical trials. SIGNIFICANCE: Clinical resistance to immunotherapy is common in breast cancer, and many patients will likely require combination therapy to maximize immunotherapeutic benefit. This study demonstrates that heterogeneous MHC-I expression drives resistance to anti–PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance
Beneficios de la quimioterapia adyuvante en los resultados de supervivencia en cáncer de mama triple negativo PT1N0M0
No full textIntroduction: Triple-negative breast cancer (TNBC) is notably an aggressive breast cancer (BC) subtype, leading to early relapse and poor prognosis. Effects of adjuvant chemotherapy among early-stage TNBC (pT1N0M0) patients remain unclear in different populations. Objectives: Our study aimed to determine the impact of adjuvant chemotherapy on overall survival (OS) and progression-free survival (PFS) within the specific subset of Peruvian pT1N0M0 TNBC patients (pT1a/b vs. pT1c). Methods: We retrospectively analyzed 2007 TNBC cases diagnosed between 2000-2014 at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru). We included only non-metastatic TNBC cases and classified them as pT1N0M0 after surgery. TNBC patients who underwent neoadjuvant chemotherapy were excluded. We describe our population according to the tumor size from the residue disease (pT1a/b vs. pT1c). We used the Kaplan-Meier method test to determine differences in survival curves for OS and PFS. A Univariate Cox proportional hazards model was used to identify risk factors for PFS. Results: Our study cohort included 124 TNBC patients. Around 65.3% (n=81) were undergoing adjuvant chemotherapy. Notably, among pT1c patients, this treatment was more prevalent compared to pT1a/b (72.1% vs. 50.0%). Survival analysis showed no significant OS benefit from chemotherapy (HR:2.46,95%CI:0.74-8.13,p=0.13). However, a marked improvement in PFS was noted exclusively in the pT1c subgroup, with patients not treated with chemotherapy offering a prognostic risk (HR:20.10,95% CI:5.54-73.10,p<0.0001). pT1a/b patients demonstrated no benefit from chemotherapy regarding progression (HR:3.07,95% CI:0.27-34.50,p=0.34). Conclusion: Our study highlights that adjuvant chemotherapy significantly improves PFS in pT1cN0M0 TNBC patients but shows no clear benefit for smaller tumors (pT1a/bN0M0). Future research should focus on personalized chemotherapy strategies in early-stage TNBC to identify predictive markers for survival
Efficacy of routine second-look endoscopy after endoscopic hemostasis in patients with acute peptic ulcer bleeding: systematic review and meta-analysis
No full textOBJECTIVE: To evaluate the efficacy of scheduled second-look endoscopy in patients with acute peptic ulcer bleeding (PUB). MATERIALS AND METHODS: We systematically search in four databases for randomized controlled trials (RCTs) that evaluated the usefulness of scheduled second-look endoscopy vs. single endoscopy in patients with PUB. Our primary outcome was rebleeding. Secondary outcomes were surgery, mortality, and the number of units of blood transfused (NUBT). All meta-analyses were performed using a random-effects model. Pooled risk ratio (RR) and mean difference (MD), with their 95% confidence intervals (CIs) were calculated for categorical and continuous outcomes, respectively. The risk of bias was assessed using the Cochrane RoB 2.0 tool, and the quality of evidence (QoE) was rated with the GRADE approach. RESULTS: Eight full-text RCTs and two RCT abstracts were included (n=1513). We did not find differences in rebleeding (RR, 0.78; 95% CI, 0.53-1.14, moderate QoE), surgery (RR, 0.58; 95% CI, 0.29-1.15, moderate QoE), mortality (RR, 0.89; 95% CI, 0.46-1.71, moderate QoE) or NUBT (MD, -0.01 units; 95% CI, -0.3 to 0.28, low QoE) between second-look and single endoscopy. Sensitivity analyses had similar results to the main analyses. CONCLUSIONS: Routine second-look endoscopy was not more efficacious than single endoscopy in patients with PUB
Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project
No full textProphages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified genome rearrangements and assessed the impact of prophage presence on bacterial gene disruption and methylome. We found that 29.5% (298) of the HpGP genomes contain prophages, of which only 32.2% (96) were complete, minimizing the burden of prophage carriage. The prevalence of H. pylori prophage sequences was variable by geography and ancestry, but not by disease status of the human host. Prophage insertion occasionally results in gene disruption that can change the global bacterial epigenome. Gene function prediction allowed the development of the first model for lysogenic-lytic cycle regulation in H. pylori. We have disclosed new prophage inactivation mechanisms that appear to occur by genome rearrangement, merger with other mobile elements, and pseudogene accumulation. Our analysis provides a comprehensive framework for H. pylori prophage biological and genomics, offering insights into lysogeny regulation and bacterial adaptation to prophages. © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.The HpGP was mainly supported by the Intramural Research Program from the US National Cancer Institute (NCI), National Institutes of Health (NIH). This work was supported in part by the intramural research programs of the US National Library of Medicine, the US National Institute on Minority Health and Health Disparities, and the US National Institute of Allergy and Infectious Diseases. FFV is funded by Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia (FCT) through project grants (project PTDC/BTM-TEC/3238/2020 and CPCA-IAC/AV/478719/2022) that partially supported this work, alongside national funds from FCT projects UIDB/04138/2020, UIDP/04138/2020, and UIDB/04046/2020 (DOI: https://doi.org/10.54499/UIDB/04046/2020). The collaborating centers for sample collection received grant support from the US NIH (P01CA116087, R01CA077955, R01DK058587 and P30DK058404 to R.M.P||P01CA028842 and R01CA190612 to K.T.W||P01CA028842, R01CA190612, K07CA125588, R03CA167773 and P30CA068485 to D.R.M||K08CA252635 to R.J.H., K22CA226395 to M.G.-P||and U54GM133807 to M.C.-C.), the German Federal Ministry of Education and Research (BMBF-0315905D, ERA-NET PathoGenoMics to P.M.), the French Association pour la Recherche Contre le Cancer (8412 to F.M.), the French Institut National du Cancer (07/3D1616/IABC-23-12/NC-NG and 2014-152 to F.M.), the Canceropole Grand Sud-Ouest (2010-08-canceropole GSO-Universite Bordeaux 2 to F.M.), the Japanese National Institutes of Health (DK62813 to Y.Y.), the Japanese Ministry of Education, Culture, Sports, Science, and Technology (18KK0266, 19H03473, 21H00346 and 22H02871 to Y.Y.), the National Fund for Innovation and Development of Science and Technology from the Ministry of Higher Education Science and Technology of the Dominican Republic (2012-2013-2A1-65 and 2015-3A1-182 to M.C.), the National Cancer Center of South Korea (2210630, I.J.C.), ArcticNet (RES0010178 to K.J.G.), the Network of Centres of Excellence of Canada, the Canadian Institutes for Health Research (MOP115031 to K.J.G.), Alberta Innovates Health Solutions (201201159 to K.J.G.), the University of Malaya-Ministry of Higher Education (UM.C/625/1/HIR/MOHE/CHAN-02 to J.V.), the Ministry of Science and Technology of Vietnam, the Kyrgyz State Medical Academy, the Italian Ministry of Health for Institutional Research, the Chilean National Fund for Health Research and Development (FONIS A19/0188, FONDECYT 1230504 and ANID-FONDAP 152220002 to A.R||ANID-FONDAP APOYO 1523A0008CONICYT-FONDAP and FONDECYT 1231773 to A.H.C.), the Chilean Cancer Prevention and Control Center, the Horizon 2020 Programme of European Union (825832, \u201CCeLac and European consortium for a personalized medicine approach to Gastric Cancer,\u201D LEGACy, to T.F.-K. and A.R.), the Funda\u00E7\u00E3o de Amparo \u00E0 Pesquisa do Estado de S\u00E3o Paulo (FAPESP; 2014/26847-0, 2018/14267-2, 2018/02972-3 to E.D.-N.), the Departamento de Ci\u00EAncia e Tecnologia (DECIT), Ministry of Health, Brazil (PRONON, SIPAR 2500.035-167/2015-23 to E.D.-N.), the Conselho Nacional de Desenvolvimento Cient\u00EDfico e Tecnol\u00F3gico (CNPq, 314344/2020-9 to E.T.-S.), the Universidad de Costa Rica (742-B9-310 and 742-90912-19 to V.R.-M.), LABGIPAT (S.D.-B.), the Hospital Cl\u00EDnica B\u00EDblica (C.C.-N.), the Greek Ministry of Culture and Education (InfeNeutra Project, NSRF 2007-2013, MIS450598, D.N.S.), the National Strategic Reference Framework Operational Program \u201CCompetitiveness, Entrepreneurship and Innovation\u201D (NSRF 2014-2020, MIS5002486, D.N.S.), the Hellenic Helicobacter pylori Study Group (2012-2016, B.M.-G.), the Hellenic Society of Gastroenterology (National Multicenter Laboratory Surveillance Studies, 2018-2019, B.M.-G.), the Ministry of Science and Technology, Executive Yuan, Taiwan (109-2314-B-002-096; MOST 111-2314-B-002-012; MOST 109-2314-B-002-090-MY3 to J.-M.L. and M.-S.W.), the National Research Foundation of Singapore, the Singapore Ministry of Health\u2019s National Medical Research Council (Open Fund-Large Collaborative Grant, MOH-OFLCG18May-0003), the University of Puerto Rico Comprehensive Cancer Center, the Fondo Nacional de Desarrollo Cientifico y Tecnologico (196-2015-FONDECYT to C.C.), Universidad Cient\u00EDfica del Sur, and Instituto Nacional de Enfermedades Neoplasicas (INEN, Peru). Our special thanks are extended to all the individuals who were the hosts of the Hp GP strain collection, who represent the human populations that bear the burden of H. pylori -associated disease, and whose biological samples serve to advance research aimed at reducing this disease burden
Hemoperitoneo secundario a tumor maligno de la vaina del nervio periférico en hígado
No full textMalignant peripheral nerve sheath tumors are frequently associated with neurofibromatosis type 1. They are usually located in the extremities or in the axial area. Its visceral location is very rare and its hepatic origin is infrequent. They tend to be aggressive with a poor response to chemotherapy and radiotherapy, so surgical management is the best treatment option. We present the case of a young man with neurofibromatosis type 1, who presented with hemoperitoneum as a complication of a malignant tumor of the peripheral nerve sheath located in the liver
Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study
No full textBackground: In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (±bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. Patients and methods: Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomly allocated 1: 1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (±bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were based on a stratified Cox regression model. Results: A total of 617 patients were randomly assigned [pembrolizumab arm, n = 308 (63.6% with bevacizumab); placebo arm, n = 309 (62.5% with bevacizumab)]. The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.56 (0.43-0.73)] and all-comer [0.57 (0.45-0.73)] populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the programmed cell death-ligand 1 combined positive score ≥1 [0.61 (0.44-0.85)] and all-comer [0.69 (0.50-0.94)] populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. Conclusion: Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use