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PURPOSE: Hematuria following post-prostatectomy radiotherapy (PPRT) is inadequately characterized. We performed a consecutive cohort study of patients treated with PPRT at our institution to characterize this complication including impact on patient-reported quality of life. MATERIALS AND METHODS: Patients with potential followup ≥4 years following PPRT were identified. Freedom from ≥grade 2 hematuria (FFG2H; macroscopic blood) was estimated using the Kaplan-Meier method. Predictors of ≥grade 2 hematuria (G2H) were assessed via log-rank tests and the Cox model. Urinary patient-reported quality of life by EPIC-26 (26-question Expanded Prostate Cancer Index Composite) was compared for patients with/without hematuria using mixed-effects regression. RESULTS: A total of 216 men received PPRT (median 68.4 Gy, IQR 68.0-68.4) from 2007 to 2016 at a median of 20 months (IQR 9-45) after prostatectomy. Median followup was 72 months (IQR 54-99). A total of 85 men developed hematuria, of whom 49 (58%) underwent cystoscopy, 13 (15%) required intervention and 26 (31%) experienced recurrent hematuria. Eight-year FFG2H was 55%. G2H was highest in men treated with anticoagulation/antiplatelet therapy (HR 3.24, p <0.001), men with bladder V65 Gy ≥43% (HR 1.97, p=0.004) and men with medication allergies (HR 1.73, p=0.049). Age <65 years (HR 0.81, p=0.374) and diabetes mellitus (HR 0.49, p=0.098) were not associated with G2H. Change in urinary continence (mean -3.5, 95% CI: 10.1, 3.1) and irritation/obstruction (mean -3.0, 95% CI: 5.8, -0.3) domain scores did not exceed the minimally clinically important difference for men with/without hematuria. CONCLUSIONS: Hematuria following PPRT is common, especially among men with medication allergies and those on anticoagulation/antiplatelet therapy; however, PPRT-related hematuria is typically self-limited. Limiting bladder V65 Gy may reduce PPRT-related hematuria.
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Hipersensibilidad , Neoplasias de la Próstata , Anciano , Anticoagulantes , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hematuria/epidemiología , Hematuria/etiología , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/cirugía , Incidencia , Masculino , Inhibidores de Agregación Plaquetaria , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Calidad de VidaRESUMEN
Purpose: To investigate whether TP53 variants may be correlated with overall survival and local control following stereotactic radiosurgery (SRS) for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Methods: Patients undergoing an initial course of SRS for NSCLC brain metastases between 1/2015 and 12/2020 were retrospectively identified. Overall survival and freedom from local intracranial progression (FFLIP) were estimated via Kaplan-Meier method. Cox models assessed TP53 variant status (pathogenic variant, PV; variant not detected, ND). Results: 255 patients underwent molecular profiling for TP53, among whom 144 (56%) had a TP53 PV. Median follow-up was 11.6 months. OS was not significantly different across TP53 status. A trend toward superior FFLIP was observed for PV (95% CI 62.9 months-NR) versus ND patients (95% CI 29.4 months-NR; p=0.06). Superior FFLIP was observed for patients with one TP53 variant versus those with TP53 ND. Conclusion: Among NSCLC patients with BMs, the potential association between TP53 status and post-SRS FFLIP warrants further investigation in a larger prospective cohort.
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PURPOSE: Chat Generative Pre-Trained Transformer (ChatGPT), an artificial intelligence program that uses natural language processing to generate conversational-style responses to questions or inputs, is increasingly being used by both patients and health care professionals. This study aims to evaluate the accuracy and comprehensiveness of ChatGPT in radiation oncology-related domains, including answering common patient questions, summarizing landmark clinical research studies, and providing literature reviews with specific references supporting current standard-of-care clinical practice in radiation oncology. METHODS AND MATERIALS: We assessed the performance of ChatGPT version 3.5 (ChatGPT3.5) in 3 areas. We evaluated ChatGPT3.5's ability to answer 28 templated patient-centered questions applied across 9 cancer types. We then tested ChatGPT3.5's ability to summarize specific portions of 10 landmark studies in radiation oncology. Next, we used ChatGPT3.5 to identify scientific studies supporting current standard-of-care practice in clinical radiation oncology for 5 different cancer types. Each response was graded independently by 2 reviewers, with discordant grades resolved by a third reviewer. RESULTS: ChatGPT3.5 frequently generated inaccurate or incomplete responses. Only 39.7% of responses to patient-centered questions were considered correct and comprehensive. When summarizing landmark studies in radiation oncology, 35.0% of ChatGPT3.5's responses were accurate and comprehensive, improving to 43.3% when provided the full text of the study. ChatGPT3.5's ability to present a list of studies related to standard-of-care clinical practices was also unsatisfactory, with 50.6% of the provided studies fabricated. CONCLUSIONS: ChatGPT should not be considered a reliable radiation oncology resource for patients or providers at this time, as it frequently generates inaccurate or incomplete responses. However, natural language programming-based artificial intelligence programs are rapidly evolving, and future versions of ChatGPT or similar programs may demonstrate improved performance in this domain.
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Procesamiento de Lenguaje Natural , Oncología por Radiación , Humanos , Inteligencia Artificial , Neoplasias/radioterapia , Atención Dirigida al PacienteRESUMEN
Purpose: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance of neurologic symptoms at the time of ITCP is poorly understood. Methods and Materials: This was a multi-institutional, retrospective cohort study from 2015 to 2020, including all patients with brain metastases completing an initial course of SRS. The primary outcome was overall survival (OS) by presence of neurologic symptoms at ITCP. OS, freedom from ITCP (FF-ITCP), and freedom from symptomatic ITCP (FF-SITCP) were assessed via Kaplan-Meier method. Cox proportional hazard models tested parameters impacting FF-ITCP and FF-SITCP. Results: Among 1383 patients, median age was 63.4 years, 55% were female, and common primaries were non-small cell lung (49%), breast (15%), and melanoma (9%). At a median follow-up of 8.72 months, asymptomatic and symptomatic ITCP were observed in 504 (36%) and 194 (14%) patients, respectively. The majority of ITCP were distant ITCP (79.5%). OS was worse with SITCP (median, 10.2 vs 17.9 months, P < .001). SITCP was associated with clinical factors including total treatment volume (P = .012), melanoma histology (P = .001), prior whole brain radiation therapy (P = .003), number of brain metastases (P < .001), interval of 1 to 2 years from primary and brain metastasis diagnosis (P = .012), controlled extracranial disease (P = .042), and receipt of pre-SRS chemotherapy (P = .015). Patients who were younger and received post-SRS chemotherapy (P = .001), immunotherapy (P < .001), and targeted or small-molecule inhibitor therapy (P < .026) had better FF-SITCP. Conclusions: In this cohort study of patients with brain metastases completing SRS, neurologic symptoms at ITCP is prognostic for OS. This data informs post-SRS surveillance in clinical practice as well as future prospective studies needed in the modern management of brain metastases.
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Importance: Clinical trials for metastatic malignant neoplasms are increasingly being extended to patients with brain metastases. Despite the preeminence of progression-free survival (PFS) as a primary oncologic end point, the correlation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survival (OS) is poorly understood for patients with brain metastases following stereotactic radiosurgery (SRS). Objective: To determine the correlation of ICP and ECP with OS among patients with brain metastases completing an initial SRS course. Design, Setting, and Participants: This multi-institutional retrospective cohort study was conducted from January 1, 2015, to December 31, 2020. We included patients who completed an initial course of SRS for brain metastases during the study period, including receipt of single and/or multifraction SRS, prior whole-brain radiotherapy, and brain metastasis resection. Data analysis was performed on November 15, 2022. Exposures: Non-OS end points included intracranial PFS, extracranial PFS, PFS, time to ICP, time to ECP, and any time to progression. Progression events were radiologically defined, incorporating multidisciplinary clinical consensus. Main Outcomes and Measures: The primary outcome was correlation of surrogate end points to OS. Clinical end points were estimated from time of SRS completion via the Kaplan-Meier method, while end-point correlation to OS was measured using normal scores rank correlation with the iterative multiple imputation approach. Results: This study included 1383 patients, with a mean age of 63.1 years (range, 20.9-92.8 years) and a median follow-up of 8.72 months (IQR, 3.25-19.68 months). The majority of participants were White (1032 [75%]), and more than half (758 [55%]) were women. Common primary tumor sites included the lung (757 [55%]), breast (203 [15%]), and skin (melanoma; 100 [7%]). Intracranial progression was observed in 698 patients (50%), preceding 492 of 1000 observed deaths (49%). Extracranial progression was observed in 800 patients (58%), preceding 627 of 1000 observed deaths (63%). Irrespective of deaths, 482 patients (35%) experienced both ICP and ECP, 534 (39%) experienced ICP (216 [16%]) or ECP (318 [23%]), and 367 (27%) experienced neither. The median OS was 9.93 months (95% CI, 9.08-11.05 months). Intracranial PFS had the highest correlation with OS (ρ = 0.84 [95% CI, 0.82-0.85]; median, 4.39 months [95% CI, 4.02-4.92 months]). Time to ICP had the lowest correlation with OS (ρ = 0.42 [95% CI, 0.34-0.50]) and the longest median time to event (median, 8.76 months [95% CI, 7.70-9.48 months]). Across specific primary tumor types, correlations of intracranial PFS and extracranial PFS with OS were consistently high despite corresponding differences in median outcome durations. Conclusions and Relevance: The results of this cohort study of patients with brain metastases completing SRS suggest that intracranial PFS, extracranial PFS, and PFS had the highest correlations with OS and time to ICP had the lowest correlation with OS. These data may inform future patient inclusion and end-point selection for clinical trials.
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Neoplasias Encefálicas , Melanoma , Radiocirugia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Estudios Retrospectivos , Neoplasias Encefálicas/secundarioRESUMEN
PURPOSE: Radiotherapy (RT) treatment at public hospitals in Nigeria is often interrupted by prolonged periods of machine breakdown because of insufficient funds for maintenance and repair. These delays have prompted the uptake of public-private partnerships (PPPs) to acquire and maintain RT equipment. This study aimed to understand Nigeria's current RT capacity and the impact of PPPs on RT availability and cost. METHODS: Eleven radiation oncologists, each representing one of the 11 RT centers in Nigeria (eight public and three private), were invited to complete a survey on the type, status, acquisition, and maintenance plan of existing RT equipment, cost incurred by patients for external-beam radiation (EBRT) and brachytherapy treatment, and number of patients treated per year on each machine. Type and status of equipment at nonresponding facilities were obtained through literature review and confirmed with the facility. RESULTS: A total of eight (81%) respondents completed the survey, all representing public centers, three of which reported PPP use. They reported 11 megavoltage units in total (seven linear accelerators [LINACs] and four Cobalt-60s) and 10 brachytherapy afterloaders. Of those, 57% (4/7) of the LINACs, 100% (4/4) of the Cobalt-60s, and 63% (7/11) of the afterloaders were in clinical use. All commissioned equipment supported by PPPs (three LINACs and one afterloader) were in operation. The public EBRT equipment were nonfunctional 35% of the year (resulting in 60% fewer patients treated per year). The PPP EBRT and afterloaders did not experience any periods of breakdown, but PPP costs were 338% higher than public equipment. CONCLUSION: This study characterizes the use of PPP as a more reliable method of RT delivery in Nigeria, albeit at higher costs.
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Braquiterapia , Oncología por Radiación , Humanos , Nigeria , Aceleradores de Partículas , Asociación entre el Sector Público-PrivadoRESUMEN
PURPOSE: In low- and middle-income countries, there has been an exponential increase in cancer incidence. According to the International Atomic Energy Agency, the biggest gap in radiotherapy availability and need is in Nigeria, where each machine serves an estimated 25.7 million people. This study aimed to characterize the barriers to radiotherapy and to identify areas for intervention. METHODS: This was a cross-sectional study conducted at the University College Hospital in Ibadan, Nigeria, from June 2017 to August 2017. Demographic, sociocultural, and infrastructural factors relating to radiotherapy were collected through a questionnaire (N = 186). Ordinal logistic regression was used to identify the factors leading to delays in referral and delays in treatment initiation. RESULTS: Patients traveled from 20 of Nigeria's 36 states. The median age was 50 years (range, 19-79 years). The most common cancers treated were breast (37.5%), cervical (16.3%), head and neck (11.9%), and prostate (10.9%). In ordinal logistic regression, sociocultural factors, including the inability to pay (odds ratio [OR], 1.99; P = .034), a bad hospital experience (OR, 7.05; P = .001), and travel time (OR, 1.36; P = .001), increased the odds of referral delay to radiotherapy. In contrast, there was no significant relationship between time to treatment initiation and sociocultural factors including age, education, and inability to pay. Infrastructural barriers, including machine breakdown (OR, 2.92; P = .001), worker strikes (OR, 2.64; P = .001), and power outages (OR, 2.81; P = .022), increased the odds of treatment delay. CONCLUSION: Although delays caused by patient factors are reported extensively, patients overcame these barriers in the hopes of curative treatment. However, staff and equipment malfunctions prevented patients from receiving timely radiotherapy. Policies aimed at addressing machine maintenance, health care worker satisfaction, and the aging power grid in Nigeria must be implemented in the future to strengthen the health care system to care for patients with cancer.
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Oncología por Radiación , Estudios Transversales , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Nigeria , Tiempo de TratamientoRESUMEN
OBJECTIVE: Wikipedia is commonly used to acquire information about various medical conditions such as chronic pain. Ideally, better online pain management content could reduce the burden of opioid use disorders. Our goal was to improve the quality of the content available on Wikipedia to make it more accurate and applicable to medical students and the general public while training medical students to practice evidence-based medicine and critically assess their sources of information. METHODS: An elective class in Neuroscience, Pain, and Opioids composed of 10 medical students met biweekly to discuss landmark and practice-changing research articles in the fields of acute pain, chronic pain, and opioid management. The professor chose Wikipedia articles relevant to this course. Three independent viewers analyzed the quality of citations, anecdotal medical content, and content value for both patients and medical professionals. As part of their coursework, students then edited the Wikipedia articles. RESULTS: Although some of the Wikipedia pain topic content (6.7% ± 2.0) was anecdotal, financially biased, or inconsistent with Western Medical Practice content, overall articles included primarily high-quality citations (85.6% ± 3.1). On a 0-5 Likert scale, students felt content would be moderately helpful for both medical students/professionals (3.4 ± 0.2) and laypersons (3.5 ± 0.2). Editing and adding citations was feasible, but novel material was often reverted. CONCLUSION: A significant amount of pain medicine content was relevant and amenable to student editing. Therefore, future use of this tactic could provide a unique opportunity to integrate evidence-based medicine into the medical curriculum and have a direct impact on the widely available medical information. Future refinement in the editorial process may also further improve online information.
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BACKGROUND: Bladder cancer is commonly diagnosed in patients ineligible for radical cystectomy or chemoradiotherapy (chemo-RT) with cisplatin or fluorouracil with mitomycin. We assessed tolerability, efficacy, and toxicity of hypofractionated radiotherapy with capecitabine in this challenging population. PATIENTS AND METHODS: Patients with high-grade urothelial bladder cancer ineligible for radical cystectomy or high-intensity chemo-RT underwent maximal transurethral resection of bladder tumor followed by capecitabine (median, 825 mg/m2 per day 2 times a day) and radiation (median, 55 Gy in 2.2 Gy per fraction). Patients underwent surveillance cystoscopy and imaging, and were evaluated for toxicity, freedom from local failure and freedom from distant metastasis, progression-free survival, and overall survival. RESULTS: Eleven patients (median age, 80 years) with localized disease (n = 7), locally advanced disease (n = 3), or local-only recurrence after cystectomy (n = 1) were treated. Four patients (35%) had an Eastern Cooperative Oncology Group performance status of 2; median Charlson comorbidity index was 5. There was 1 acute grade 3 genitourinary event (9%), 6 acute grade 3 hematologic events (55%) of lymphopenia, and no acute grade 4 or higher events or hospitalizations. Ten patients (91%) completed radiotherapy, while 4 patients (36%) temporarily discontinued capecitabine. The complete response rate in the bladder was 64%. Two patients (18%) experienced late grade 1/2 genitourinary toxicities, and 1 (9%) experienced a transient late grade 4 genitourinary toxicity. With a median follow-up of 16.6 months, overall survival, progression-free survival, freedom from local failure, and freedom from distant metastasis at 1 year were 82%, 55%, 100%, and 55%, respectively, and at 2 years were 61%, 41%, 80%, and 55%, respectively. CONCLUSION: Hypofractionated chemo-RT was well tolerated and was associated with a high rate of local control in this comorbid population, thus providing a treatment option for select bladder cancer patients.
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Antimetabolitos Antineoplásicos/uso terapéutico , Capecitabina/uso terapéutico , Quimioradioterapia/mortalidad , Hospitalización/estadística & datos numéricos , Hipofraccionamiento de la Dosis de Radiación , Neoplasias Urológicas/terapia , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Urológicas/patologíaRESUMEN
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC). Results Fifty-one patients with RCC (N = 22) were enrolled, including 30 (59%) with one or more lines of prior VEGF-targeting therapy. Five dose-limiting toxicities, including fatigue (n = 2), thrombocytopenia (n = 2), and elevated AST/ALT (n = 1), were observed with schedule A; one dose-limiting toxicity was observed (elevated AST/ALT) was observed with schedule B. Grade ≥ 3 related adverse events included fatigue (16%), thrombocytopenia (16%), and neutropenia (10%). The recommended phase II dose was established as abexinostat 45 mg/m2 twice a day administered per schedule B plus pazopanib 800 mg/d. Objective response rate was 21% overall and 27% in the RCC subset. Median duration of response was 9.1 months (1.2 to > 49 months). Eight patients (16%) had durable control of disease for > 12 months. Durable tumor regressions were observed in seven (70%) of 10 patients with pazopanib-refractory disease, including one patients with RCC with ongoing response > 3.5 years. Peripheral blood histone acetylation and HDAC2 gene expression were associated with durable response to treatment. Conclusion Abexinostat is well tolerated in combination with pazopanib, allowing prolonged exposure and promising durable responses in pazopanib- and other VEGF inhibitor-refractory tumors, which supports epigenetically mediated reversal of treatment resistance.
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Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Renales/tratamiento farmacológico , Acetilación , Adulto , Anciano , Alanina Transaminasa/sangre , Inhibidores de la Angiogénesis/administración & dosificación , Aspartato Aminotransferasas/sangre , Benzofuranos/administración & dosificación , Benzofuranos/sangre , Benzofuranos/farmacocinética , Carcinoma de Células Renales/genética , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Resistencia a Medicamentos , Epigénesis Genética , Fatiga/inducido químicamente , Femenino , Expresión Génica , Histona Desacetilasa 2/genética , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/sangre , Inhibidores de Histona Desacetilasas/farmacocinética , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/administración & dosificación , Ácidos Hidroxámicos/sangre , Ácidos Hidroxámicos/farmacocinética , Indazoles , Neoplasias Renales/genética , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neutropenia/inducido químicamente , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Trombocitopenia/inducido químicamente , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Adulto JovenRESUMEN
Purpose: The PARP inhibitor (PARPi) talazoparib may potentiate activity of chemotherapy and toxicity in cells vulnerable to DNA damage.Experimental Design: This phase I study evaluated the safety, tolerability, pharmacokinetics, and efficacy of talazoparib and carboplatin. Pharmacokinetic modeling explored associations between DNA vulnerability and hematologic toxicity.Results: Twenty-four patients (eight males; 16 females) with solid tumors were enrolled in four cohorts at 0.75 and 1 mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, every 2 weeks or every 3 weeks), including 14 patients (58%) with prior platinum treatment. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the MTD was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). After cycle 2's dose, delays/reductions were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond 4 months, three of which had known mutations in DNA repair pathways. Pharmacokinetic toxicity modeling suggests that after three cycles of carboplatin AUC 1.5 every 3 weeks and talazoparib 1 mg daily, neutrophil counts decreased 78% [confidence interval (CI), 87-68] from baseline in gBRCA carriers and 63% (CI, 72-55) in noncarriers (P < 0.001). Pharmacokinetic toxicity modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status, may improve the benefit/risk ratio of combination therapy.Conclusions: Carboplatin and talazoparib showed efficacy in DNA damage mutation carriers, but hematologic toxicity was more pronounced in gBRCA carriers. Carboplatin is best combined with intermittent talazoparib dosing differentiated by germline and somatic DNA damage mutation carriers. Clin Cancer Res; 23(21); 6400-10. ©2017 AACR.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Carboplatino/administración & dosificación , Neoplasias/tratamiento farmacológico , Ftalazinas/administración & dosificación , Adulto , Anciano , Carboplatino/efectos adversos , Carboplatino/farmacocinética , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Mutación de Línea Germinal/genética , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/patología , Ftalazinas/efectos adversos , Ftalazinas/farmacocinética , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
UNLABELLED: Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%-97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful. SIGNIFICANCE: Precision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases.