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1.
JCO Oncol Pract ; : OP2400070, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959441

RESUMO

PURPOSE: Less than half of the patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)-based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P = .026), and received NCCN guideline-concordant care (89.8% v 78.2%, P = .035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team-focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites.

2.
JCO Oncol Pract ; : OP2400356, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39024535

RESUMO

PURPOSE: Germline genetic testing (GT) is recommended for all patients with pancreatic ductal adenocarcinoma (PDAC), but the traditional clinical genetics infrastructure is limited in addressing the unique needs of this population. We describe the integration of point of care (POC) GT into routine clinical practice for all patients with PDAC at an academic medical center. METHODS: We developed a clinical POC workflow that leverages electronic health record (EHR) tools and behavioral nudges to enhance the sustainability and scalability of our previously described research-based POC model. For each of the research and clinical POC cohorts, we calculated the percentage of eligible patients who underwent GT. We used Wilcoxon rank-sum and Pearson's chi-squared tests to compare patients who did and did not undergo GT. We conducted surveys among oncology clinicians to evaluate the acceptability, appropriateness, and feasibility of the clinical POC model. RESULTS: The research POC cohort included 905 patients, of whom 694 (76.7%) underwent GT. The clinical POC cohort included 148 patients, of whom 126 (85.1%) underwent GT. Patients who underwent GT in the research POC cohort were significantly younger (median age, 67.0 v 70.9 years; P = .031) and more likely to be White (82.1% v 68.7%; P < .001) and commercially insured (41.8% v 28.0%; P < .001) compared with those who did not; there were no significant differences between GT groups in the clinical POC cohort. Oncology clinicians found the clinical POC model to be acceptable (mean 4.4/5), appropriate (4.6/5), feasible (4.0/5), and have a positive impact on their patients (4.9/5). CONCLUSION: A clinical POC model leveraging EHR tools and behavioral nudges is acceptable, appropriate, feasible, and associated with a >85% GT rate among patients with PDAC.

3.
J Natl Cancer Inst ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38745430

RESUMO

BACKGROUND: Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-out-pocket (OOP) costs. The ASCO Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. METHODS: We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide de-identified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication. RESULTS: We included 8,524 patients with incident claims for eight oral TCDs with nine first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (IQR $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10,118.79 (IQR $6,365.95-$10,600.37) for an incident 28-day TCD supply. Total spending increased $1,083.56 for each 10-point increase in NHB score (95% CI $1,050.27-$1,116.84, p < .01 for H0=$0). CONCLUSION: Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs.

4.
JCO Oncol Pract ; 20(4): 483-490, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38237102

RESUMO

PURPOSE: Capecitabine is an oral chemotherapy used to treat many gastrointestinal cancers. Its complex dosing and narrow therapeutic index make medication adherence and toxicity management crucial for quality care. METHODS: We conducted a pilot study of PENNY-GI, a mobile phone text messaging-based chatbot that leverages algorithmic surveys and natural language processing to promote medication adherence and toxicity management among patients with gastrointestinal cancers on capecitabine. Eligibility initially included all capecitabine-containing regimens but was subsequently restricted to capecitabine monotherapy because of challenges in integrating PENNY-GI with radiation and intravenous chemotherapy schedules. We used design thinking principles and real-time data on safety, accuracy, and usefulness to make iterative refinements to PENNY-GI with the goal of minimizing the proportion of text messaging exchanges with incorrect medication or symptom management recommendations. All patients were invited to participate in structured exit interviews to provide feedback on PENNY-GI. RESULTS: We enrolled 40 patients (median age 64.5 years, 52.5% male, 62.5% White, 55.0% with colorectal cancer, 50.0% on capecitabine monotherapy). We identified 284 of 3,895 (7.3%) medication-related and 13 of 527 (2.5%) symptom-related text messaging exchanges with incorrect recommendations. In exit interviews with 24 patients, participants reported finding the medication reminders reliable and user-friendly, but the symptom management tool was too simplistic to be helpful. CONCLUSION: Although PENNY-GI provided accurate recommendations in >90% of text messaging exchanges, we identified multiple limitations with respect to the intervention's generalizability, usefulness, and scalability. Lessons from this pilot study should inform future efforts to develop and implement digital health interventions in oncology.


Assuntos
Telefone Celular , Neoplasias Gastrointestinais , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Projetos Piloto , Adesão à Medicação
5.
Ann Surg ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37830225

RESUMO

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

6.
JCO Clin Cancer Inform ; 7: e2300024, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37639653

RESUMO

PURPOSE: To develop an electronic health record (EHR)-based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS: Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION: We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Sistemas de Apoio a Decisões Clínicas , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Estudos Transversais , Registros Eletrônicos de Saúde , Eletrônica
7.
J Natl Compr Canc Netw ; 21(4): 351-358.e4, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37015340

RESUMO

BACKGROUND: Germline genetic testing (GT) for BRCA1/2 is instrumental in identifying patients with breast and ovarian cancers who are eligible for PARP inhibitors (PARPi). Little is known about recent trends and determinants of GT since PARPi were approved for these patients. PATIENTS AND METHODS: We performed a retrospective cohort study of patients in a nationwide electronic health record (EHR)-derived oncology-specific database with the following GT eligibility criteria: breast cancer diagnosed at age ≤45 years, triple-negative breast cancer diagnosed at age ≤60 years, male breast cancer, or ovarian cancer. GT within 1 year of diagnosis was assessed and stratified by tumor type. Multivariable log-binomial regressions estimated adjusted relative risks (RRs) of GT by patient and tumor characteristics. RESULTS: Among 2,982 eligible patients with breast cancer, 56.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.08; 95% CI, 1.05-1.11, for each year), independent of when PARPi were approved for BRCA1/2-mutated metastatic breast cancer in January 2018. In multivariable analyses, older age (RR, 0.93; 95% CI, 0.90-0.96, for every 5 years) and Medicare coverage (RR, 0.69; 95% CI, 0.49-0.96 vs commercial insurance) were associated with less GT. Among 5,563 eligible patients with ovarian cancer, 35.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.11; 95% CI, 1.07-1.14, for each year) that accelerated after approval of PARPi for BRCA1/2-mutated, chemotherapy-refractory ovarian cancer in December 2014 (RR, 1.42; 95% CI, 1.19-1.70). Older age (RR, 0.95; 95% CI, 0.93-0.97, for every 5 years) and Black or African American race (RR, 0.80; 95% CI, 0.65-0.98 vs White race) were associated with less GT. CONCLUSIONS: GT remains underutilized nationwide among patients with breast and ovarian cancers. Although GT has increased over time, significant disparities by age, race, and insurance status persist. Additional work is needed to design, implement, and evaluate strategies to ensure that all eligible patients receive GT.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias de Mama Triplo Negativas , Estados Unidos/epidemiologia , Humanos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medicare , Proteína BRCA1/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Testes Genéticos , Neoplasias de Mama Triplo Negativas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
8.
Genet Med ; 24(11): 2338-2350, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36107166

RESUMO

PURPOSE: Integrating genomic data into the electronic health record (EHR) is key for optimally delivering genomic medicine. METHODS: The PennChart Genomics Initiative (PGI) at the University of Pennsylvania is a multidisciplinary collaborative that has successfully linked orders and results from genetic testing laboratories with discrete genetic data in the EHR. We quantified the use of the genomic data within the EHR, performed a time study with genetic counselors, and conducted key informant interviews with PGI members to evaluate the effect of the PGI's efforts on genetics care delivery. RESULTS: The PGI has interfaced with 4 genetic testing laboratories, resulting in the creation of 420 unique computerized genetic testing orders that have been used 4073 times to date. In a time study of 96 genetic testing activities, EHR use was associated with significant reductions in time spent ordering (2 vs 8 minutes, P < .001) and managing (1 vs 5 minutes, P < .001) genetic results compared with the use of online laboratory-specific portals. In key informant interviews, multidisciplinary collaboration and institutional buy-in were identified as key ingredients for the PGI's success. CONCLUSION: The PGI's efforts to integrate genomic medicine into the EHR have substantially streamlined the delivery of genomic medicine.


Assuntos
Atenção à Saúde , Registros Eletrônicos de Saúde , Humanos , Genômica , Laboratórios , Software
9.
Front Oncol ; 12: 859846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865463

RESUMO

Background: Fluoropyrimidines (fluorouracil [5-FU], capecitabine) and irinotecan are commonly prescribed chemotherapy agents for gastrointestinal (GI) malignancies. Pharmacogenetic (PGx) testing for germline DPYD and UGT1A1 variants associated with reduced enzyme activity holds the potential to identify patients at high risk for severe chemotherapy-induced toxicity. Slow adoption of PGx testing in routine clinical care is due to implementation barriers, including long test turnaround times, lack of integration in the electronic health record (EHR), and ambiguity in test cost coverage. We sought to establish PGx testing in our health system following the Exploration, Preparation, Implementation, Sustainment (EPIS) framework as a guide. Our implementation study aims to address barriers to PGx testing. Methods: The Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI) study is a non-randomized, pragmatic, open-label implementation study at three sites within a major academic health system. Eligible patients with a GI malignancy indicated for treatment with 5-FU, capecitabine, or irinotecan will undergo PGx testing prior to chemotherapy initiation. Specimens will be sent to an academic clinical laboratory followed by return of results in the EHR with appropriate clinical decision support for the care team. We hypothesize that the availability of a rapid turnaround PGx test with specific dosing recommendations will increase PGx test utilization to guide pharmacotherapy decisions and improve patient safety outcomes. Primary implementation endpoints are feasibility, fidelity, and penetrance. Exploratory analyses for clinical effectiveness of genotyping will include assessing grade ≥3 treatment-related toxicity using available clinical data, patient-reported outcomes, and quality of life measures. Conclusion: We describe the formative work conducted to prepare our health system for DPYD and UGT1A1 testing. Our prospective implementation study will evaluate the clinical implementation of this testing program and create the infrastructure necessary to ensure sustainability of PGx testing in our health system. The results of this study may help other institutions interested in implementing PGx testing in oncology care. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04736472, identifier [NCT04736472].

10.
Cancer ; 128(9): 1853-1862, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35119688

RESUMO

BACKGROUND: Timely targeted treatment initiation can be challenging because additional biomarker testing is needed for eligibility. The authors hypothesized that timely targeted treatment improves survival relative to nontimely initiation in metastatic HER2+ gastroesophageal adenocarcinoma (GEA). METHODS: The authors performed a retrospective cohort study of metastatic HER2+ GEA treated with first-line (1L) systemic therapy from January 2011 to December 2017 using a nationwide electronic health record-derived deidentified database. Timely targeted treatment-trastuzumab initiation within 14 days after starting 1L chemotherapy-was assessed as a time-varying exposure. Nontimely targeted treatment included patients who initiated trastuzumab after 14 days or who lacked documentation of receiving trastuzumab. Extended Cox regressions compared overall survival (OS) and progression-free survival (PFS) between timely and nontimely groups. RESULTS: A total of 320 patients were included; 59.1% received timely trastuzumab. Relative to nontimely initiation, timely trastuzumab was associated with significantly higher OS (2-year OS, 32.1% vs 15.3%; adjusted hazard ratio [HR], 0.67; 95% CI, 0.51-0.88) and PFS (2-year PFS, 9.2% vs 3.7%; adjusted HR, 0.71; 95% CI, 0.55-0.93). Results remained similar in sensitivity analyses 1) using alternative "timeliness" definitions up to 70 days after starting 1L chemotherapy, 2) comparing any trastuzumab, regardless of timing of initiation, to no trastuzumab, and 3) excluding patients lacking documentation of receiving trastuzumab. CONCLUSIONS: Improved survival was observed among metastatic HER2+ GEA patients treated with trastuzumab versus those who were not, regardless of timing of initiation. Although these results reassure clinicians that modest targeted treatment delays may not be detrimental to outcomes, efforts should still ensure that all metastatic HER2+ GEA patients receive trastuzumab.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Receptor ErbB-2/genética , Estudos Retrospectivos , Trastuzumab/uso terapêutico , Resultado do Tratamento
11.
BMC Cancer ; 22(1): 47, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996412

RESUMO

BACKGROUND: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. METHODS: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. RESULTS: Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. CONCLUSIONS: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study.


Assuntos
Antineoplásicos/administração & dosagem , Tomada de Decisão Clínica , Neoplasias Gastrointestinais/tratamento farmacológico , Testes Farmacogenômicos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oncologistas/estatística & dados numéricos , Padrões de Prática Médica , Pesquisa Qualitativa
13.
Cancer ; 127(14): 2562-2570, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33730386

RESUMO

BACKGROUND: Anti human epidermal growth factor receptor 2 (anti-HER2) therapy with trastuzumab improves overall survival in patients with advanced, HER2-positive gastroesophageal adenocarcinoma (GEA) and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine practice. METHODS: The authors performed a cross-sectional study of patients who had advanced GEA diagnosed between January 2011 and June 2019 in a nationwide electronic health record-derived database. The annual prevalences of both timely HER2 testing (defined within 21 days after advanced diagnosis) and timely trastuzumab initiation (defined within 14 days after a positive HER2 result) were calculated. Log-binomial regressions estimated adjusted prevalence ratios comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics. RESULTS: In total, the cohort included 6032 patients with advanced GEA of whom 1007 were HER2-positive. Between 2011 and 2019, timely HER2 testing increased from 22.4% to 44.5%, whereas timely trastuzumab initiation remained stable at 16.3%. No appreciable differences in timely testing or trastuzumab initiation were noted by age, sex, race, or insurance status. Compared with patients who had metastatic disease at diagnosis, patients who had early stage GEA who did not undergo surgery were less likely to receive timely HER2 testing and trastuzumab initiation (testing prevalence ratio, 0.69; 95% CI, 0.64-0.75; treatment prevalence ratio, 0.32; 95% CI, 0.18-0.56), as were patients with early stage disease who subsequently developed a distant recurrence (testing prevalence ratio, 0.56; 95% CI, 0.47-0.65; treatment prevalence ratio, 0.61; 95% CI, 0.24-1.55). CONCLUSIONS: In patients with advanced GEA, guideline-recommended HER2 testing and anti-HER2 therapy remain underused. Uptake may improve with universal HER2 testing regardless of stage.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos Transversais , Humanos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia , Trastuzumab/uso terapêutico
15.
Pharmacotherapy ; 40(11): 1108-1129, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32985005

RESUMO

Gastrointestinal (GI) malignancies are among the most commonly diagnosed cancers worldwide. Despite the introduction of targeted and immunotherapy agents in the treatment landscape, cytotoxic agents, such as fluoropyrimidines and irinotecan, remain as the cornerstone of chemotherapy for many of these tumors. Pharmacogenetics (PGx) is a rapidly evolving field that accounts for interpatient variability in drug metabolism to predict therapeutic response and toxicity. Given the significant incidence of severe treatment-related adverse events associated with cytotoxic agents, utilizing PGx can allow clinicians to better anticipate drug tolerability while minimizing treatment interruptions or delays. In this review, the PGx profiles of drug-gene pairs with potential impact in GI malignancy therapy - DPYD-5-fluorouracil/capecitabine and UGT1A1-irinotecan - and the available clinical evidence of their roles in reducing severe adverse events are discussed. Considerations for clinical implementation, such as optimal laboratory workflows, electronic health record integration, and stakeholder engagement, as well as provider education, are addressed. Last, exploratory PGx markers in GI malignancy treatment are described. As the PGx knowledge base rapidly evolves, pharmacists will be vital in leveraging their pharmacology knowledge and clinical skills to implement PGx testing in the clinic.


Assuntos
Antineoplásicos/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Glucuronosiltransferase/genética , Humanos , Farmacogenética , Testes Farmacogenômicos
16.
Clin Colorectal Cancer ; 19(2): e49-e57, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32165040

RESUMO

BACKGROUND: Metastatic colorectal cancer (CRC) outcomes continue to improve, but they vary significantly by race and ethnicity. We hypothesize that these disparities arise from unequal access to care. MATERIALS AND METHODS: The Harris Health System (HHS) is an integrated health delivery network that provides medical care to the underserved, predominantly minority population of Harris County, Texas. As the largest HHS facility and an affiliate of Baylor College of Medicine's Dan L. Duncan Comprehensive Cancer Center, Ben Taub Hospital (BTH) delivers cancer care through multidisciplinary subspecialty that prioritize access to care, adherence to evidence-based clinical pathways, integration of supportive services, and mitigation of financial toxicity. We performed a retrospective analysis of minority patients diagnosed with and treated for metastatic CRC at BTH between January 2010 and December 2012. Kaplan-Meier survival curves were compared with survival curves from randomized control trials reported during that time period. RESULTS: We identified 103 patients; 40% were black, 49% were Hispanic, and 12% were Asian or Middle Eastern. Thirty-five percent reported a language other than English as their preferred language. Seventy-four percent of patients with documented coverage status were uninsured. Eighty-four percent of patients received standard chemotherapy with a clinician-reported response rate of 63%. Overall survival for BTH patients undergoing chemotherapy was superior to that of subjects enrolled in the CRYSTAL (Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer) trial (median, 24.0 vs. 19.9 months; P = .014). CONCLUSION: HHS provides a health delivery infrastructure through which minority patients with socioeconomic challenges experience clinical outcomes comparable with highly selected patients enrolled in randomized control trials. Efforts to resolve CRC disparities should focus on improving access of at-risk populations to high-quality comprehensive cancer care.


Assuntos
Neoplasias Colorretais/mortalidade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Provedores de Redes de Segurança/estatística & dados numéricos , Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Asiático/estatística & dados numéricos , Neoplasias Colorretais/economia , Neoplasias Colorretais/terapia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Provedores de Redes de Segurança/economia , Fatores Socioeconômicos , População Branca/estatística & dados numéricos
17.
Cancer ; 123(24): 4895-4902, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28881383

RESUMO

BACKGROUND: Although hospitalized patients with advanced cancer have a low chance of surviving cardiopulmonary resuscitation (CPR), the processes by which they change their code status from full code to do not resuscitate (DNR) are unknown. METHODS: We conducted a mixed-methods study on a prospective cohort of hospitalized patients with advanced cancer. Two physicians used a consensus-driven medical record review to characterize processes that led to code status order transitions from full code to DNR. RESULTS: In total, 1047 hospitalizations were reviewed among 728 patients. Admitting clinicians did not address code status in 53% of hospitalizations, resulting in code status orders of "presumed full." In total, 275 patients (26.3%) transitioned from full code to DNR, and 48.7% (134 of 275 patients) of those had an order of "presumed full" at admission; however, upon further clarification, the patients expressed that they had wished to be DNR before the hospitalization. We identified 3 additional processes leading to order transition from full code to DNR acute clinical deterioration (15.3%), discontinuation of cancer-directed therapy (17.1%), and education about the potential harms/futility of CPR (15.3%). Compared with discontinuing therapy and education, transitions because of acute clinical deterioration were associated with less patient involvement (P = .002), a shorter time to death (P < .001), and a greater likelihood of inpatient death (P = .005). CONCLUSIONS: One-half of code status order changes among hospitalized patients with advanced cancer were because of full code orders in patients who had a preference for DNR before hospitalization. Transitions due of acute clinical deterioration were associated with less patient engagement and a higher likelihood of inpatient death. Cancer 2017;123:4895-902. © 2017 American Cancer Society.


Assuntos
Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Neoplasias/mortalidade , Neoplasias/patologia , Ordens quanto à Conduta (Ética Médica) , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/métodos , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Avaliação das Necessidades , Invasividade Neoplásica/patologia , Neoplasias/terapia , Estudos Prospectivos , Medição de Risco , Assistência Terminal/legislação & jurisprudência
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