What Complexity Science Predicts About the Potential of Artificial Intelligence/Machine Learning to Improve Primary Care.

Primary care physicians are likely both excited and apprehensive at the prospects for artificial intelligence (AI) and machine learning (ML). Complexity science may provide insight into which AI/ML applications will most likely affect primary care in the future. AI/ML has successfully diagnosed some diseases from digital images, helped with administrative tasks such as writing notes in the electronic record by converting voice to text, and organized information from multiple sources within a health care system. AI/ML has less successfully recommended treatments for patients with complicated single diseases such as cancer; or improved diagnosing, patient shared decision making, and treating patients with multiple comorbidities and social determinant challenges. AI/ML has magnified disparities in health equity, and almost nothing is known of the effect of AI/ML on primary care physician-patient relationships. An intervention in Victoria, Australia showed promise where an AI/ML tool was used only as an adjunct to complex medical decision making. Putting these findings in a complex adaptive system framework, AI/ML tools will likely work when its tasks are limited in scope, have clean data that are mostly linear and deterministic, and fit well into existing workflows. AI/ML has rarely improved comprehensive care, especially in primary care settings, where data have a significant number of errors and inconsistencies. Primary care should be intimately involved in AI/ML development, and its tools carefully tested before implementation; and unlike electronic health records, not just assumed that AI/ML tools will improve primary care work life, quality, safety, and person-centered clinical decision making.

Impact of a Medical Scribe Program on the Educational Trajectory of Prehealth and Underrepresented in Medicine Students.

BACKGROUND AND OBJECTIVES: Sparse research exists on evaluating the effects of medical scribing programs on the educational trajectory of prehealth students. This study assesses the impact of the Stanford Medical Scribe Fellowship (COMET) on its prehealth participants' educational goals, preparation for graduate training, and acceptance into health professional schools. METHODS: We distributed a 31-question survey with both closed- and open-ended questions to 96 alumni. The survey collected participant demographics, self-reported underrepresented in medicine (URM) status, pre-COMET clinical experiences and educational goals, application to and acceptance at health professional schools, and perceived impact of COMET on their educational trajectory. SPSS was used to complete the analyses. RESULTS: The survey had a 97% (93/96) completion rate. Among all respondents, 69% (64/93) applied to a health professional school and 70% (45/64) were accepted. Among URM respondents, 68% (23/34) applied to a health professional school and 70% (16/23) were accepted. Overall acceptance rates for MD/DO and PA/NP programs were 51% (24/47) and 61% (11/18), respectively. URM acceptance rates for MD/DO and PA/NP programs were 43% (3/7) and 58% (7/12), respectively. For current or recently graduated health professional school respondents, 97% (37/38) "strongly agreed" or "agreed" that COMET helped them succeed in their training. CONCLUSIONS: COMET is associated with a positive impact on the educational trajectory of its prehealth participants and a higher acceptance rate into health professional schools than the national rates for both overall and URM applicants. Scribing programs may serve as pipeline development and help increase the diversity of the future health care workforce.

Competencies for the Use of Artificial Intelligence in Primary Care.

The artificial intelligence (AI) revolution has arrived for the health care sector and is finally penetrating the far-reaching but perpetually underfinanced primary care platform. While AI has the potential to facilitate the achievement of the Quintuple Aim (better patient outcomes, population health, and health equity at lower costs while preserving clinician well-being), inattention to primary care training in the use of AI-based tools risks the opposite effects, imposing harm and exacerbating inequalities. The impact of AI-based tools on these aims will depend heavily on the decisions and skills of primary care clinicians; therefore, appropriate medical education and training will be crucial to maximize potential benefits and minimize harms. To facilitate this training, we propose 6 domains of competency for the effective deployment of AI-based tools in primary care: (1) foundational knowledge (what is this tool?), (2) critical appraisal (should I use this tool?), (3) medical decision making (when should I use this tool?), (4) technical use (how do I use this tool?), (5) patient communication (how should I communicate with patients regarding the use of this tool?), and (6) awareness of unintended consequences (what are the "side effects" of this tool?). Integrating these competencies will not be straightforward because of the breadth of knowledge already incorporated into family medicine training and the constantly changing technological landscape. Nonetheless, even incremental increases in AI-relevant training may be beneficial, and the sooner these challenges are tackled, the sooner the primary care workforce and those served by it will begin to reap the benefits.

A Systematic Review of the Cost-Effectiveness of Stereotactic Radiation Therapy for Cancer Oligometastases.

It is crucial to economically justify the use of promising therapies such as stereotactic ablative radiotherapy (SABR) for oligometastatic disease (OMD). The goal of this systematic review was to provide a summative evaluation of publications that analyzed the cost-effectiveness (CE) of SABR for OMD. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided methodology, PubMed and Embase were searched for modeling-based CE studies for various forms of limited metastatic disease. Only full publications that specifically compared SABR with a systemic therapy-based approach were included. In total, 9 studies met inclusion criteria; 4 pertained to OMD with mixed histologies, 2 to oligometastatic non-small cell lung cancer, 1 to pulmonary OMD, 1 to liver OMD, and 1 to low-volume oligorecurrent castration-sensitive prostate cancer. All but 1 investigation illustrated that SABR was cost-effective for the studied population (or a subpopulation); of these studies, the incremental CE ratios for SABR (when reported) ranged from $28,000/quality-adjusted life-year (QALY) to $55,000/QALY. Of studies that reported the probability of SABR being cost-effective at common willingness-to-pay values, the median (range) probability of achieving CE was roughly 61% (30%-88%) at a $50,000/QALY threshold and 78% (31%-100%) at a $100,000/QALY threshold. Taken together, the available evidence suggests that SABR appears to be a cost-effective approach for OMD, which has implications for value-based oncologic practice and construction of future health policies. However, reassessment is required in the context of modern systemic therapies (eg, immunotherapy) as well as long-term follow-up of existing and newly reported randomized trials. Prudent patient selection remains the single most important factor influencing the CE of SABR for OMD.

A Clinician's Guide to Artificial Intelligence (AI): Why and How Primary Care Should Lead the Health Care AI Revolution.

Artificial intelligence (AI) in health care is the future that is already here. Despite its potential as a transformational force for primary care, most primary care providers (PCPs) do not know what it is, how it will impact them and their patients, and what its key limitations and ethical pitfalls are. This article is a beginner's guide to health care AI, written for the frontline PCP. Primary care-as the dominant force at the base of the health care pyramid, with its unrivaled interconnectedness to every part of the health system and its deep relationship with patients and communities-is the most uniquely suited specialty to lead the health care AI revolution. PCPs can advance health care AI by partnering with technologists to ensure that AI use cases are relevant and human-centered, applying quality improvement methods to health care AI implementations, and advocating for inclusive and ethical AI that combats, rather than worsens, health inequities.

Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments.

PURPOSE: The main purpose of this work was to generate and validate the dosimetric accuracy of proton beams of dimensions that are appropriate for in vivo small animal and in vitro ultrahigh dose rate (FLASH) radiotherapy experiments using a synchrotron-based treatment delivery system. This study was performed to enable future investigations of the relevance of a spread-out Bragg peak (SOBP) under FLASH conditions. METHODS: The spill characteristics of the small field fixed horizontal beam line were modified to deliver accelerated protons in times as short as 2 ms and to control the dose delivered. A Gaussian-like transverse beam profile was transformed into a square uniform one at FLASH dose rates, while avoiding low-dose regions, a crucial requirement to protect normal tissue during FLASH irradiation. Novel beam-shaping devices were designed using Monte Carlo techniques to produce up to about 6 cm3 of uniform dose in SOBPs while maximizing the dose rate. These included a scattering foil, a conical flattening filter to maximize the flux of protons into the region of interest, energy filters, range compensators, and collimators. The shapes, sizes, and positions of the components were varied to provide the required field sizes and SOBPs. RESULTS: The designed and fabricated devices were used to produce 10-, 15-, and 20-mm diameter, circular field sizes and 10-, 15-, and 20-mm SOBP modulation widths at uniform physical dose rates of up to 375 Gy/s at the center of the SOBP and a minimum dose rate of about 255 Gy/s at the entrance, respectively, in cylindrical volumes. The flatness of lateral dose profiles at the center could be adjusted to within ±1.5% at the center of the SOBP. Assessment of systematic uncertainties, such as impact of misalignments and positioning uncertainties, was performed using simulations, and the results were used to provide appropriate adjustments to ensure high-accuracy FLASH beam delivery for both in vitro and in vivo preclinical experiments. CONCLUSIONS: It is feasible to use synchrotron-generated proton beams of sufficient dimensions for FLASH radiobiology experiments. We expect to use the system we developed to acquire in vitro and in vivo small animal FLASH radiobiology data as a function of dose, dose rate, oxygen content, and linear energy transfer to help us understand the underlying mechanisms of the FLASH phenomenon.

Exploring the synergy of radiative coupling and substrate undercut in arrayed gold nanodisks for economical, ultra-sensitive label-free biosensing.

We report radiatively coupled arrayed gold nanodisks on invisible substrate (AGNIS) as a cost-effective, high-performance platform for nanoplasmonic biosensing. By substrate undercut, the electric field distribution around the nanodisks has been restored to as if the nanodisks were surrounded by a single medium, thereby provides analyte accessibility to otherwise buried enhanced electric field. The AGNIS substrate has been fabricated by wafer-scale nanosphere lithography without the need for costly lithography. The LSPR blue-shifting behavior synergistically contributed by radiative coupling and substrate undercut have been investigated for the first time, which culminates in a remarkable refractive index sensitivity increase from 207 nm/RIU to 578 nm/RIU. The synergy also improves surface sensitivity to monolayer neutravidin-biotin binding from 7.4 nm to 20.3 nm with the limit of detection (LOD) of neutravidin at 50 fM, which is among the best label-free results reported to date on this specific surface binding reaction. As a potential cancer diagnostic application, extracellular vesicles such as exosomes excreted by cancer and normal cells were measured with a LOD within 112-600 (exosomes/µL), which would be sufficient in many clinical applications. Using CD9, CD63, and CD81 antibodies, label-free profiling has shown increased expression of all three surface antigens in cancer-derived exosomes. This work demonstrates, for the first time, strong synergy of arrayed radiative coupling and substrate undercut can enable economical, ultrasensitive biosensing in the visible light spectrum where high-quality, low-cost silicon detectors are readily available for point-of-care applications.

Efficient and Economical Targeted Insertion in Plant Genomes via Protoplast Regeneration.

Versatile genome editing can be facilitated by the insertion of DNA sequences into specific locations. Current protocols involving CRISPR and Cas proteins rely on low efficiency homology-directed repair or non-homologous end joining with modified double-stranded DNA oligonucleotides as donors. Our simple protocol eliminates the need for expensive equipment, chemical and enzymatic donor DNA modification, or plasmid construction by using polyethylene glycol-calcium to deliver non-modified single-stranded DNA oligonucleotides and CRISPR-Cas9 ribonucleoprotein into protoplasts. Plants regenerated via edited protoplasts achieved targeted insertion frequencies of up to 50% in Nicotiana benthamiana and 13.6% in rapid cycling Brassica oleracea without antibiotic selection. Using a 60 nt donor containing 27 nt in each homologous arm, 6/22 regenerated N. benthamiana plants showed targeted insertions, and one contained a precise insertion of a 6 bp HindIII site. The inserted sequences were transmitted to the next generation and invite the possibility of future exploration of versatile genome editing by targeted DNA insertion in plants.

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial.

PURPOSE: Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements. RESULTS: Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L. CONCLUSIONS: Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.

Five Years' Experience With a Medical Scribe Fellowship: Shaping Future Health Professions Students While Addressing Provider Burnout.

Professional burnout has reached epidemic levels among U.S. medical providers. One key driver is the burden of clinical documentation in the electronic health record, which has given rise to medical scribes. Despite the demonstrated benefits of scribes, many providers-especially those in academic health systems-have been unable to make an economic case for them. With the aim of creating a cost-effective scribe program in which premedical students gain skills that better position them for professional schooling, while providers at risk of burnout obtain documentation support, the authors launched the Clinical Observation and Medical Transcription (COMET) Program in June 2015 at Stanford University School of Medicine. COMET is a new type of postbaccalaureate premedical program that combines an apprenticeship-like scribing experience and a package of teaching, advising, application support, and mentored scholarship that is supported by student tuition. Driven by strong demand from both participants and faculty, the program grew rapidly during its first 5 years (2015-2020). Program evaluations indicated high levels of satisfaction among participants and faculty with their mentors and mentees, respectively; that participants felt the experience better positioned them for professional schooling; and that faculty reported improved joy of practice. In summary, tuition-supported medical scribe programs, like COMET, appear to be feasible and cost-effective. The COMET model may have the potential to help shape future health professions students, while simultaneously combating provider burnout. While scalability and generalizability remain uncertain, this model may be worth exploring at other institutions.

Impact of a Family Medicine Minor Procedure Service on Cost of Care for a Health Plan.

BACKGROUND AND OBJECTIVES: Academic medical centers (AMC) are among some of the most expensive places to provide care. One way to cut costs is by decreasing unnecessary referrals to specialists for procedures that can be provided by well-trained primary care physicians. Our goal is to measure the financial impact of an office-based minor procedure service driven entirely by family physicians. METHODS: We examined claims data for procedures performed on patients insured under our AMC's home-grown accountable care organization-style health plan (Stanford Health Care Alliance [SHCA]). Descriptive statistics was used to compare the volume and cost of procedures performed by family medicine (FM) versus specialty care (SC). We preformed a subanalysis of SC procedures to explore the degree to which consultation and facility fees increased costs for SC. We used mathematical modeling to estimate the impact on cost of care if procedures were shifted from SC to FM and to calculate a return on investment (ROI). RESULTS: Our data set examined 6,974 outpatient procedures performed on SHCA patients from 2016-2018 at a cost of $5,263,720 to SHCA. FM performed 6% of procedures at an average cost of $236 per procedure, while SC performed 94% of procedures at an average cost of $787 per procedure. FM saved money for all 12 types of skin, musculoskeletal, and reproductive procedures assessed; the average saved per procedure was $551. This represents a 70% cost savings. ROI was 2.33; for every $1 spent on FM procedures, SHCA saved $2.33. CONCLUSION: A family medicine minor procedure service significantly lowered health spending at our AMC.

Alternative Multidisciplinary Management Options for Locally Advanced NSCLC During the Coronavirus Disease 2019 Global Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is currently accelerating. Patients with locally advanced NSCLC (LA-NSCLC) may require treatment in locations where resources are limited, and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk of severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Although guiding data is scarce, we present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are the following: (1) reduce the number of visits to a health care facility, (2) reduce the risk of exposure to severe acute respiratory syndrome-coronavirus-2, (3) attenuate the immunocompromising effects of lung cancer therapies, and (4) provide effective oncologic therapy. Patients with resectable disease can be treated with definitive nonoperative management if surgical resources are limited or the risks of perioperative care are high. Nonoperative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be on the basis of patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually, cancer therapies may be withheld until symptoms have resolved with negative viral test results. The risk of severe treatment-related morbidity and mortality is increased for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Commercial Insurance Coverage of Advanced Radiation Therapy Techniques Compared With American Society for Radiation Oncology Model Policies.

PURPOSE: This study aimed to compare and contrast the American Society for Radiation Oncology (ASTRO) model policies (MPs) for intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), stereotactic ablative radiation therapy (SABR), and proton beam therapy (PBT) with the coverage policies constructed by 5 of the largest publicly available commercial insurers throughout the United States (ie, Aetna, Anthem, Cigna, Humana, and United Healthcare). METHODS AND MATERIALS: Appropriate indications for IMRT, SRS, SABR, and PBT by disease site (and particular clinical setting thereof) were extracted from the most recently published ASTRO MPs and published coverage policies (2019 editions) of the 5 carriers. After tabulation, concordance between ASTRO MPs and insurance policies were calculated for each modality. RESULTS: All 5 insurer policies supported IMRT for neoplasms of the central nervous system, head/neck, hepatopancreaticobiliary, anal, and prostate cancers. The least covered diseases were retroperitoneal tumors (n = 0 carriers) and bladder cancer (n = 1). For SRS, all carriers covered benign brain tumors, brain metastases, arteriovenous malformations, and trigeminal neuralgia. None of the insurance carriers covered SRS for medically refractory epilepsy. For SABR, primary liver, lung, and low- or intermediate-risk prostate cancer were covered by all insurers, and none allowed SABR for primary biliary neoplasms. Only one insurance carrier each covered SABR for primary/metastatic adrenal disease and primary renal cancer. All carriers approved PBT for ocular melanoma, skull base tumors, and pediatric malignancies. The ASTRO MPs listed 4 PBT scenarios (ie, spinal disease, retroperitoneal sarcoma, head/neck neoplasms, and patients with genetic radiosensitivity syndromes) not covered by any insurer. Concordance between insurance carriers and ASTRO MPs was 67.8% for IMRT, 72.0% for SRS, 58.4% for SABR, and 41.8% for PBT (P = .005). CONCLUSIONS: Coverage guidelines for IMRT, SRS, SABR, and PBT vary across 5 major insurance providers and may be substantially discordant compared with ASTRO coverage guidelines. There remain several specific areas where ongoing and future dialogues between ASTRO members, payers, and policymakers remain essential.

Factors Associated With Age Disparities Among Cancer Clinical Trial Participants.

Importance: Seminal investigation 2 decades ago alerted the oncology community to age disparities in participation in cooperative group trials; less is known about whether these disparities persist in industry-funded research. Objective: To characterize the age disparities among trial enrollees on randomized clinical trials (RCTs) of common cancers in clinical oncology and identify factors associated with wider age imbalances. Data Sources: Phase 3 clinical oncology RCTs were identified through ClinicalTrials.gov. Study Selection: Multiarm RCTs assessing a therapeutic intervention for patients with breast, prostate, colorectal, or lung cancer (the 4 most common cancer disease sites) were included. Data Extraction and Synthesis: Trial data were extracted from ClinicalTrials.gov. Trial screening and parameter identification were independently performed by 2 individuals. Data were analyzed in 2018. Main Outcomes and Measures: The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was determined for each trial. Results: Three hundred two trials met inclusion criteria. The trials collectively enrolled 262 354 participants; 249 trials (82.5%) were industry-funded. For all trials, the trial median age of trial participants was a mean of 6.49 years younger than the population median age (95% CI, -7.17 to -5.81 years; P < .001). Age disparities were heightened among industry-funded trials compared with non-industry-funded trials (mean DMA, -6.84 vs -4.72 years; P = .002). Enrollment criteria restrictions based on performance status or age cutoffs were associated with age disparities; however, industry-funded trials were not more likely to use these enrollment restrictions than non-industry-funded trials. Age disparities were also larger among trials that evaluated a targeted systemic therapy and among lung cancer trials. Linear regression modeling revealed a widening gap between trial and population median ages over time at a rate of -0.19 years annually (95% CI, -0.37 to -0.01 years; P = .04). Conclusions and Relevance: Age disparities between trial participants and the incident disease population are pervasive across trials and appear to be increasing over time. Industry sponsorship of trials is associated with heightened age imbalances among trial participants. With an increasing role of industry funding among cancer trials, efforts to understand and address age disparities are necessary to ensure generalizability of trial results as well as equity in trial access.

Ten Ways Artificial Intelligence Will Transform Primary Care.

Artificial intelligence (AI) is poised as a transformational force in healthcare. This paper presents a current environmental scan, through the eyes of primary care physicians, of the top ten ways AI will impact primary care and its key stakeholders. We discuss ten distinct problem spaces and the most promising AI innovations in each, estimating potential market sizes and the Quadruple Aims that are most likely to be affected. Primary care is where the power, opportunity, and future of AI are most likely to be realized in the broadest and most ambitious scale. We propose how these AI-powered innovations must augment, not subvert, the patient-physician relationship for physicians and patients to accept them. AI implemented poorly risks pushing humanity to the margins; done wisely, AI can free up physicians' cognitive and emotional space for patients, and shift the focus away from transactional tasks to personalized care. The challenge will be for humans to have the wisdom and willingness to discern AI's optimal role in twenty-first century healthcare, and to determine when it strengthens and when it undermines human healing. Ongoing research will determine the impact of AI technologies in achieving better care, better health, lower costs, and improved well-being of the workforce.

Providing Specialty Care for the Poor and Underserved at Student-Run Free Clinics in the San Francisco Bay Area.

This report describes the model of specialty clinics implemented at Stanford University's two student-run free clinics, Arbor Free Clinic and Pacific Free Clinic, in the San Francisco Bay Area. We describe our patient demographic characteristics and the specialty services provided. We discuss challenges in implementing specialty care at student-run free clinics.

Addition of Definitive Radiotherapy to Chemotherapy in Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer.

Background: Management of metastatic (M1) nasopharyngeal cancer (NPC) is controversial; data suggest high overall survival (OS) rates with definitive chemoradiotherapy (CRT). Herein, we evaluated OS in patients with M1 NPC undergoing chemotherapy alone versus CRT. Methods: The National Cancer Data Base was queried for M1 NPC cases. Patients undergoing no/unknown chemotherapy and/or with unknown/nondefinitive radiotherapy (RT) doses (<60 Gy) were excluded. Logistic regression analysis ascertained clinical factors associated with RT administration. Kaplan-Meier analysis evaluated OS between both cohorts; Cox proportional hazards modeling assessed factors associated with OS. Survival was then evaluated between matched populations using inverse-probability-weighted regression adjustment. OS between groups was also measured in patients surviving ≥1 and ≥3 years to address bias from poor-prognostic subsets (eg, widely disseminated disease), and those receiving CRT ≤30 and ≤60 days of each other (surrogates for concurrent CRT) versus >30 and >60 days (sequential) of each other. Results: Of 555 patients, 296 (53%) received chemotherapy alone and 259 (47%) underwent CRT. Patients undergoing CRT more often had private insurance (P=.001) and lived in areas with higher education levels (P=.028). Median OS in the chemotherapy-only and CRT cohorts were 13.7 and 25.8 months, respectively (P<.001); differences persisted between matched populations (P<.001). On multivariate analysis, receipt of additional RT independently predicted for improved OS (P<.001). OS differences between cohorts remained apparent when evaluating patients surviving for ≥1 (P<.001) and ≥3 (P=.002) years. Patients who received concurrent or sequential CRT displayed improved OS over those receiving chemotherapy alone, for both the 30-day (P<.001) and 60-day cutoffs (P<.001). Conclusions: Patients with M1 NPC undergoing definitive RT and chemotherapy experienced higher survival than those receiving chemotherapy alone. Risk stratification and patient selection for such combined modality interventions is critical.

Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders.

The emergence of direct-acting antiviral (DAA) therapies and noninvasive measures of liver fibrosis has streamlined the management of patients with chronic hepatitis C virus (HCV) infection. DAA therapy is associated with a significantly higher rate of sustained virologic response (SVR) compared to interferon-based therapies. Concomitantly, validated noninvasive measures of fibrosis allow evaluation of patients for therapy without an invasive liver biopsy. Noninvasive measures of fibrosis can be classified as serologic tests or imaging modalities. Several serologic tests have shown robust reliability and clinical applicability. Similarly, imaging modalities such as vibration-controlled transient elastography and magnetic resonance elastography can be used to assess liver stiffness and correlate with fibrosis. Combinations of serologic and imaging tests further improve accuracy compared to an individual modality. The availability of noninvasive fibrosis measures coupled with high SVR rates has shifted the paradigm in the management of HCV infection in the DAA era. Although these noninvasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy, use of these measures in monitoring fibrosis regression after HCV eradication is currently limited. Furthermore, for patients with pretreatment cirrhosis, the association between fibrosis regression after successful therapy and the risk of hepatocellular carcinoma (HCC) over time is unclear. There are no guidelines on long-term fibrosis monitoring and HCC surveillance after SVR is achieved. This article summarizes the current data on the applications of noninvasive methods to measure hepatic fibrosis and portal hypertension in HCV. In addition, a road map is provided for monitoring patients with advanced fibrosis after HCV eradication.