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INTRODUCTION: Electronic health record (EHR) discontinuity (missing out-of-network encounters) can lead to information bias. We sought to construct an algorithm that identifies high EHR-continuity among oncology patients. METHODS: Using a linked Medicare-EHR database and regression, we sought to 1) measure how often Medicare claims for outpatient encounters were substantiated by visits recorded in the EHR, and 2) predict continuity ratio, defined as the yearly proportion of outpatient encounters reported to Medicare that were captured by EHR data. The prediction model’s performance was evaluated with the coefficient of determination and Spearman’s correlation. We quantified variable misclassification by decile of continuity ratio using standardized difference and sensitivity. RESULTS: A total of 79,678 subjects met all eligibility criteria. Predicted and observed continuity was highly correlated (σ(Spearman) = 0.86). On average across all variables measured, MSD was reduced by a factor of 1/7(th) and sensitivity was improved 35-fold comparing subjects in the highest vs. lowest decile of CR. CONCLUSION: In the oncology population, restricting EHR-based study cohorts to subjects with high continuity may reduce misclassification without greatly impacting representativeness. Further work is needed to elucidate the best manner of implementing continuity prediction rules in cohort studies.

PURPOSE: The COVID-19 pandemic forced rapid adoption of telemedicine (TM) for breast oncology visits in the United States, but the appropriate role of postpandemic TM is uncertain. We sought to understand physician and advance practice practitioner perspectives on the use of TM for outpatient breast cancer care through an electronically administered survey. METHODS: Breast medical oncology clinicians at two academic cancer centers and five satellite locations affiliated with the Dana Farber Cancer Institute and the Massachusetts General Cancer Center were invited to respond to a 21-question survey administered in September 2021 about clinicians' perceptions and attitudes toward TM during the previous 12 months. RESULTS: Of the 71 survey invitations, 51 clinicians (36 physicians and 15 advance practice practitioners) provided survey responses (response rate = 72%). Ninety-two percent of respondents (n = 47) agreed that TM visits enhance patient care. Ninety-two percent of respondents (n = 46) also agreed that TM is valuable for early-stage breast cancer follow-up visits. Most respondents felt that there was no difference between TM and face-to-face (F2F) visits when it came to patient adherence, ease of ordering tests, ease of accessing patient records, and workflow outside of the visit (82%, 82%, 78%, and 53%, respectively). Fifty-one percent of respondents (n = 26) said that TM was better for timely access to follow-up appointments. Most respondents said that F2F visits were better for seeing physical problems, personal connection with patients, overall quality of visits, and patient-physician communication (100%, 75%, 65%, and 63%, respectively). CONCLUSION: Breast clinicians believe that TM is a valuable tool to enhance outpatient breast cancer care. TM was felt to be appropriate for routine follow-up visits and second opinion consultations and is as good as or better than F2F visits for several routine aspects of breast cancer care.

Background Guidelines for follow-up after locoregional breast cancer treatment recommend imaging for distant metastases only in the presence of patient signs and/or symptoms. However, guidelines have not been updated to reflect advances in imaging, systemic therapy, or the understanding of biological subtype. We assessed the association between mode of distant recurrence detection and survival. Methods In this observational study, a stage-stratified random sample of women with stage II-III breast cancer in 2006-2007 and followed through 2016 was selected, including up to 10 women from each of 1217 Commission on Cancer facilities (n = 10 076). The explanatory variable was mode of recurrence detection (asymptomatic imaging vs signs and/or symptoms). The outcome was time from initial cancer diagnosis to death. Registrars abstracted scan type, intent (cancer-related vs not, asymptomatic surveillance vs not), and recurrence. Data were merged with each patient’s National Cancer Database record. Results Surveillance imaging detected 23.3% (284 of 1220) of distant recurrences (76.7%, 936 of 1220 by signs and/or symptoms). Based on propensity-weighted multivariable Cox proportional hazards models, patients with asymptomatic imaging compared with sign and/or symptom detected recurrences had a lower risk of death if estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative (triple negative; hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.54 to 0.99), or HER2 positive (HR = 0.51, 95% CI = 0.33 to 0.80). No association was observed for ER- or PR-positive, HER2-negative (HR = 1.14, 95% CI = 0.91 to 1.44) cancers. Conclusions Recurrence detection by asymptomatic imaging compared with signs and/or symptoms was associated with lower risk of death for triple-negative and HER2-positive, but not ER- or PR-positive, HER2-negative cancers. A randomized trial is warranted to evaluate imaging surveillance for metastases results in these subgroups.

The National Cancer Institute Division of Cancer Control and Population Science hosted a virtual conference on the Future of Cancer Health Economics Research and included a presentation from a workgroup that considered current challenges and future directions in health economics research centered on cancer treatment. The workgroup identified 3 broad categories of focus: data limitations, opportunities for training for clinicians and health economists interested in collaboration, and the need for prospective economic study of cancer treatment. Within these areas of focus, the workgroup recommended the following: improvement of the availability of key economic measures in data available to researchers, creation of more comprehensive datasets robust to insurance type or coverage, development of cancer care health economics research-focused symposia, instituting clear mechanisms to support integration of economic analyses alongside clinical trials, development of standardized methods to measure the cost of cancer care to health-care systems and patients, and development of standardized evaluations that include measures of social determinants of health.

Background: In 2017, DNA mismatch repair/microsatellite instability (MMR/MSI) testing was nationally recommended for advanced colorectal cancers based on favorable immune checkpoint inhibitor responses among patients with MMR-deficient/MSI-high tumors. Methods: Patients ages ≥20-years-old presenting with stage IV colorectal adenocarcinoma from 2010 to 2017 were identified from the National Cancer Database. 2017 was the latest year with available testing utilization data. Patient, tumor, socioeconomic, and care setting characteristics were evaluated for association with upfront MMR/MSI testing in 2017 using multivariable logistic regression and average adjusted predicted probabilities (%AAP). Results: Among 72,830 stage IV colorectal cancers, upfront MMR/MSI testing levels increased from 16.4% in 2010 to 56.4% in 2017. For patients diagnosed in 2017 (i.e., following national recommendations, n = 10,022), testing levels were lower for older patients (Padj < 0.001), and were independent of patients' race/ethnicity and insurance status. Patients from the poorest quartile of households received less testing [49.6%AAP, 99.9% confidence interval (CI) 45.5–53.7] than patients from the 3rd (56.9%AAP, 99.9% CI, 53.3–60.6; Padj < 0.001) or 4th quartiles (57.6%AAP, 99.9% CI, 54.3–60.9; Padj < 0.001). Although testing levels improved most at community programs, they remained lower in 2017 (46.6%AAP, 99.9% CI, 41.0–52.1) compared with academic/NCI-designated comprehensive cancer centers (62.8%AAP, 99.9% CI, 59.7–65.8; Padj < 0.001). Conclusions: Upfront MMR/MSI testing utilization for patients with advanced colorectal cancer has increased but there is still substantial need for optimization. Testing utilization disproportionately lagged for patients who were older, from the poorest quartile of households, or managed at community cancer programs. Impact: Our findings indicate opportunities for improving rates of MMR/MSI testing and reporting, possibly through incorporation into quality control and accreditation metrics.

Adjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer.We developed a decision model to simulate a hypothetical cohort of 65-year-old patients with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative under 2 different interventions: (1) test for the absence of CDX2 expression followed by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no adjuvant chemotherapy for any patient. We derived disease progression parameters, adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Sensitivity analyses were conducted.Testing for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797 discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients remains cost-effective for hazard ratios of0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence.Testing tumors of patients with stage II colon cancer for CDX2 and administration of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions.

Background Combination irinotecan and cetuximab is approved for irinotecan-refractory metastatic colorectal cancer (mCRC). It is unknown if adding bevacizumab improves outcomes. Patients and Methods In this multicenter, randomized, double-blind, placebo-controlled phase II trial, patients with irinotecan-refractory RAS-wildtype mCRC and no prior anti-EGFR therapy were randomized to cetuximab 500 mg/m2, bevacizumab 5 mg/kg, and irinotecan 180 mg/m2 (or previously tolerated dose) (CBI) versus cetuximab, irinotecan, and placebo (CI) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results The study closed early after the accrual of 36 out of a planned 120 patients due to changes in funding. Nineteen patients were randomized to CBI and 17 to CI. Baseline characteristics were similar between arms. Median PFS was 9.7 versus 5.5 months for CBI and CI, respectively (1-sided log-rank P = .38; adjusted hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.25-1.66). Median OS was 19.7 versus 10.2 months for CBI and CI (1-sided log-rank P = .02; adjusted HR = 0.41; 95% CI, 0.15-1.09). ORR was 36.8% for CBI versus 11.8% for CI (P = .13). Grade 3 or higher AEs occurred in 47% of patients receiving CBI versus 35% for CI (P = .46). Conclusion In this prematurely discontinued trial, there was no significant difference in the primary endpoint of PFS between CBI and CI. There was a statistically significant improvement in OS in favor of CBI compared with CI. Further investigation of CBI for the treatment of irinotecan-refractory mCRC is warranted. Clinical Trial Registration: NCT02292758

PURPOSE To inform precision oncology, methods are needed to use electronic health records (EHRs) to identify patients with cancer who are experiencing clinical inflection points, consistent with worsening prognosis or a high propensity to change treatment, at specific time points. Such patients might benefit from real-time screening for clinical trials. METHODS Using serial unstructured imaging reports for patients with solid tumors or lymphoma participating in a single-institution precision medicine study, we trained a deep neural network natural language processing (NLP) model to dynamically predict patients' prognoses and propensity to start new palliative-intent systemic therapy within 30 days. Model performance was evaluated using Harrell's c-index (for prognosis) and the area under the receiver operating characteristic curve (AUC; for new treatment and new clinical trial enrollment). Associations between model outputs and manual annotations of cancer progression were also evaluated using the AUC. RESULTS A deep NLP model was trained and evaluated using 302,688 imaging reports for 16,780 patients. In a held-out test set of 34,770 reports for 1,952 additional patients, the model predicted survival with a c-index of 0.76 and initiation of new treatment with an AUC of 0.77. Model-generated prognostic scores were associated with annotation of cancer progression on the basis of manual EHR review (n = 1,488 reports for 110 patients with lung or colorectal cancer) with an AUC of 0.78, and predictions of new treatment were associated with annotation of cancer progression on the basis of manual EHR review with an AUC of 0.84. CONCLUSION Training a deep NLP model to identify clinical inflection points among patients with cancer is feasible. This approach could identify patients who may benefit from real-time targeted clinical trial screening interventions at health system scale.

To accelerate cancer research that correlates biomarkers with clinical endpoints, methods are needed to ascertain outcomes from electronic health records at scale. Here, we train deep natural language processing (NLP) models to extract outcomes for participants with any of 7 solid tumors in a precision oncology study. Outcomes are extracted from 305,151 imaging reports for 13,130 patients and 233,517 oncologist notes for 13,511 patients, including patients with 6 additional cancer types. NLP models recapitulate outcome annotation from these documents, including the presence of cancer, progression/worsening, response/improvement, and metastases, with excellent discrimination (AUROC > 0.90). Models generalize to cancers excluded from training and yield outcomes correlated with survival. Among patients receiving checkpoint inhibitors, we confirm that high tumor mutation burden is associated with superior progression-free survival ascertained using NLP. Here, we show that deep NLP can accelerate annotation of molecular cancer datasets with clinically meaningful endpoints to facilitate discovery., To accelerate cancer research that correlates biomarkers with clinical endpoints, methods are needed to ascertain outcomes from electronic health records at scale. Here, the authors train natural language processing to extract outcomes for participants in a precision oncology study.

Background Racial and ethnic minority status, structural racism, low educational attainment, and poverty are consistently associated with cancer disparities and with higher rates of incarceration. The objective of this scoping review is to conduct a qualitative synthesis of the literature on cancer prevalence, incidence, mortality, and disparities in these outcomes for incarcerated and formerly incarcerated patients, as this literature is fragmented and heterogenous. Methods This scoping review included Bureau of Justice Statistics reports and searched PubMed in May 2021 for all English language studies published between 1990 and 30 April 2021, that reported on cancer prevalence, incidence, or mortality for incarcerated or formerly incarcerated individuals in the United States. Results Twenty studies were selected. Data on cancer prevalence and incidence were scarce but suggested that incarcerated and formerly incarcerated patients have a similar overall risk of cancer diagnosis as the general population, but elevated risk of certain cancers such as cervical, lung, colorectal, and hepatocellular carcinoma for which effective prevention and screening interventions exist. Cancer mortality data in state and local jails as well as prisons were robust and suggests that both incarcerated and formerly incarcerated patients have higher cancer mortality than the general population. Conclusions Incarcerated and formerly incarcerated patients likely have a higher risk of dying from cancer than the general population, but important gaps in our knowledge about the extent and drivers of disparities for this population remain. Additional research is needed to guide interventions to reduce cancer disparities for patients experiencing incarceration., This scoping review finds that individuals who are currently or formerly incarcerated in prison have higher cancer mortality than the general population. However, important knowledge gaps remain that must be addressed to inform targeted interventions to reduce cancer disparities in prisons and in the community.

ImportanceThe risk of recurrence in patients with locally advanced rectal cancer has historically been determined after surgery, relying on pathologic variables. A growing number of patients are being treated without surgery, and their risk of recurrence needs to be calculated differently.ObjectiveTo develop a dynamic calculator for estimating the probability of recurrence-free survival (RFS) in patients with rectal cancer who undergo total neoadjuvant therapy (TNT) (induction systemic chemotherapy and chemoradiotherapy) and either surgery or watch-and-wait management.Design, Setting, and ParticipantsThis cohort study included patients who presented with stage II or III rectal cancer between June 1, 2009, and March 1, 2015, at a comprehensive cancer center. Conditional modeling was incorporated into a previously validated clinical calculator to allow the probability of RFS to be updated based on whether the patient remained in watch-and-wait management or underwent delayed surgery. Data were analyzed from November 2021 to March 2022.ExposureTNT followed by immediate surgery or watch-and-wait management with the possibility of delayed surgery.Main Outcomes and MeasuresRFS, concordance index, calibration curves.ResultsOf the 302 patients in the cohort, 204 (68%) underwent surgery within 3 months from TNT completion (median [range] age, 51 [22-82] years; 78 [38%] women), 54 (18%) underwent surgery more than 3 months from TNT completion (ie, delayed surgery; median [range] age, 62 [31-87] years; 30 [56%] female), and 44 (14%) remained in watch-and-wait management as of April 21, 2021 (median [range] age, 58 [32-89] years; 16 [36%] women). Among patients who initially opted for watch-and-wait management, migration to surgery due to regrowth or patient choice occurred mostly within the first year following completion of TNT, and RFS did not differ significantly whether surgery was performed 3.0 to 5.9 months (73%; 95% CI, 52%-92%) vs 6.0 to 11.9 months (71%; 95% CI, 51%-99%) vs more than 12.0 months (70%; 95% CI, 49%-100%) from TNT completion (P = .70). RFS for patients in the watch-and-wait cohort at 12 months from completion of TNT more closely resembled patients who had undergone surgery and had a pathologic complete response than the watch-and-wait cohort at 3 months from completion of TNT. Accordingly, model performance improved over time, and the concordance index increased from 0.62 (95% CI, 0.53-0.71) at 3 months after TNT to 0.66 (95% CI, 0-0.75) at 12 months.Conclusions and RelevanceIn this cohort study of patients with rectal cancer, the clinical calculator reliably estimated the likelihood of RFS for patients who underwent surgery immediately after TNT, patients who underwent delayed surgery after entering watch-and-wait management, and patients who remained in watch-and-wait management. Delayed surgery following attempted watch-and-wait did not appear to compromise oncologic outcomes. The risk calculator provided conditional survival estimates at any time during surveillance and could help physicians counsel patients with rectal cancer about the consequences of alternative treatment pathways and thereby support informed decisions that incorporate patients’ preferences.

Often electronic tools are built with English proficient (EP) patients in mind. Cancer patients with limited English proficiency (LEP) experience gaps in care and are at risk for excess toxic effects if they are unable to effectively communicate with their care team.To evaluate whether electronic patient-reported outcome tools (ePROs) built to improve health outcomes for EP patients might also be acceptable for LEP patients in the context of oral cancer-directed therapies (OCDT).This qualitative study was conducted at a single National Cancer Institute-designated comprehensive cancer center. In 2019, English-speaking and Spanish-speaking LEP patients with cancer receiving oral chemotherapies were recruited to participate in a qualitative focus group examining patient attitudes toward ePROs and electronic tools that are used to manage adherence and symptoms related to oral therapies. Six focus groups were held for EP patients and 1 for Spanish-speaking LEP patients. LEP was defined as patients who self-identified as needing an interpreter to navigate the health care system. Data analysis was performed April through June of 2019.Enrolled patients participated in a focus group lasting approximately 90 minutes.The perspectives of patients with cancer treated with oral chemotherapies on integrating ePROs into their care management.Among the 46 participants included in the study, 46 (100%) were White, 10 (22%) were Latinx Spanish-speaking, 43 (93%) were female, and 37 (80%) were aged at least 50 years or older. Among the 6 focus groups with 6 to 8 EP patients (ranging from 6 to 8 participants) and 1 focus group with 10 Spanish-speaking LEP patients, this qualitative study found that EP and LEP patients had different levels of acceptability of using technology and ePRO tools to manage their OCDT. EP patients felt generally positive toward OCDT and were not generally interested in using electronic tools to manage their care. LEP patients generally disliked OCDT and welcomed the use of technology for health management, particularly when addressing gaps in symptom management by their oncology clinicians.Although most electronic interventions target EP patients, these findings reveal the willingness of LEP patients to participate in technology-based interventions. Expanding ePROs to LEP patients may help to manage gaps in communication about treatment and potential adverse events because of the willingness of LEP patients to use ePRO tools to manage their health. This qualitative assessment is a strategic step in determining the resources needed to narrow the digital health gap and extend the value of PROs to the LEP oncology population.

IMPORTANCE: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene. OBJECTIVE: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes. DESIGN, SETTING, AND PARTICIPANTS: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021. INTERVENTIONS: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care. MAIN OUTCOMES AND MEASURES: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available. RESULTS: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P = .02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P = .002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P = .002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P = .009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P = .003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P = .006). CONCLUSIONS AND RELEVANCE: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03249090

PURPOSE Collecting patient-reported outcomes (PROs) can improve symptom control and quality of life, enhance doctor-patient communication, and reduce acute care needs for patients with cancer. Digital solutions facilitate PRO collection, but without robust electronic health record (EHR) integration, effective deployment can be hampered by low patient and clinician engagement and high development and deployment costs. The important components of digital PRO platforms have been defined, but procedures for implementing integrated solutions are not readily available. METHODS As part of the NCI's IMPACT consortium, six health care systems partnered with Epic to develop an EHR-integrated, PRO-based electronic symptom management program (eSyM) to optimize postoperative recovery and well-being during chemotherapy. The agile development process incorporated user-centered design principles that required engagement from patients, clinicians, and health care systems. Whenever possible, the system used validated content from the public domain and took advantage of existing EHR capabilities to automate processes. RESULTS eSyM includes symptom surveys on the basis of the PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE) plus two global wellness questions; reminders and symptom self-management tip sheets for patients; alerts and symptom reports for clinicians; and population management dashboards. EHR dependencies include a secure Health Insurance Portability and Accountability Act-compliant patient portal; diagnosis, procedure and chemotherapy treatment plan data; registries that identify and track target populations; and the ability to create reminders, alerts, reports, dashboards, and charting shortcuts. CONCLUSION eSyM incorporates validated content and leverages existing EHR capabilities. Build challenges include the innate technical limitations of the EHR, the constrained availability of site technical resources, and sites' heterogenous EHR configurations and policies. Integration of PRO-based symptom management programs into the EHR could help overcome adoption barriers, consolidate clinical workflows, and foster scalability and sustainability. We intend to make eSyM available to all Epic users.

BACKGROUND Smoking, the most common risk factor for bladder cancer (BC), is associated with increased complications after radical cystectomy (RC), poorer oncologic outcomes, and higher mortality. The authors hypothesized that the effect of smoking on the probability of major complications increases with increasing age among patients who undergo RC. METHODS The authors analyzed the American College of Surgeons National Surgical Quality Improvement Program database (2011-2017), identified all patients undergoing RC using Current Procedural Terminology codes, and formed two groups according to smoking status (active smoker and nonsmoker [included former and never-smokers]). Patient characteristics and 30-day postoperative complications using the Clavien-Dindo Classification (CDC) were assessed. A multivariable logistic regression model was constructed that included age, sex, race, body mass index, operative time, comorbidities, chemotherapy status, and type of diversion with major complications (CDC ≥III) as the outcome variable, and explored the interaction between age and smoking status. RESULTS A total of 10,528 patients underwent RC, including 22.8% who were active smokers. The authors identified an interaction between age and smoking status (P = .045). Older patients were found to experience a stronger smoking effect than younger patients with regard to the probability of major complications. The risk of a major complication was the same for 50-year-old nonsmokers and smokers, but it increased from 17.8% to 21.7% for 70-year-old nonsmokers and smokers, respectively (P < .001). CONCLUSIONS Up to 20% of patients who undergo RC are active smokers, and these individuals have an increased risk of major complications. The effect of smoking is stronger with increasing age; the difference with regard to complications for smokers versus nonsmokers was found to increase substantially, wherein older smokers are at an especially high risk of complications.

PURPOSE There is increasing interest in implementing digital systems for remote monitoring of patients’ symptoms during routine oncology practice. Information is limited about the clinical utility and user perceptions of these systems. METHODS PRO-TECT is a multicenter trial evaluating implementation of electronic patient-reported outcomes (ePROs) among adults with advanced and metastatic cancers receiving treatment at US community oncology practices (ClinicalTrials.gov identifier: NCT03249090 ). Questions derived from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are administered weekly by web or automated telephone system, with alerts to nurses for severe or worsening symptoms. To elicit user feedback, surveys were administered to participating patients and clinicians. RESULTS Among 496 patients across 26 practices, the majority found the system and questions easy to understand (95%), easy to use (93%), and relevant to their care (91%). Most patients reported that PRO information was used by their clinicians for care (70%), improved discussions with clinicians (73%), made them feel more in control of their own care (77%), and would recommend the system to other patients (89%). Scores for most patient feedback questions were significantly positively correlated with weekly PRO completion rates in both univariate and multivariable analyses. Among 57 nurses, most reported that PRO information was helpful for clinical documentation (79%), increased efficiency of patient discussions (84%), and was useful for patient care (75%). Among 39 oncologists, most found PRO information useful (91%), with 65% using PROs to guide patient discussions sometimes or often and 65% using PROs to make treatment decisions sometimes or often. CONCLUSION These findings support the clinical utility and value of implementing digital systems for monitoring PROs, including the PRO-CTCAE, in routine cancer care.

Background: Among patients diagnosed with stage IA non–small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. Methods: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. Results: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70–74 years, 1.13 for 75–79 years, 1.31 for 80–84 years, and 1.46 for ≥85 years compared with 65–69 years; all PPPP1 vs score of 0; PConclusions: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

Background Historically, older patients with advanced lung cancer have often received no systemic treatment. Immunotherapy has improved outcomes in clinical trials, but its dissemination and implementation at the population level is not well‐understood. Methods A retrospective cohort study of patients with stage IV non‐small cell lung cancer (NSCLC) diagnosed age 66 or older from 2012 to 2015 was conducted using SEER‐Medicare. Treatment patterns within one year of diagnosis were ascertained. Outcomes included delivery of (a) any systemic therapy; (b) any second‐line infusional therapy, following first‐line infusional therapy; and (c) any second‐line immunotherapy, following first‐line infusional therapy. Trends in care patterns associated with second‐line immunotherapy approvals in 2015 were assessed using generalized additive models. Sociodemographic and clinical predictors of treatment were explored using logistic regression. Results Among 10 303 patients, 5173 (50.2%) received first‐line systemic therapy, with little change between the years 2012 (47.5%) and 2015 (50.3%). Among 3943 patients completing first‐line infusional therapy, the proportion starting second‐line infusional treatment remained stable from 2012 (30.5%) through 2014 (32.9%), before increasing in 2015 (42.4%) concurrent with second‐line immunotherapy approvals. Factors associated with decreased utilization of any therapy included age, black race, Medicaid eligibility, residence in a high‐poverty area, nonadenocarcinoma histology, and comorbidity; factors associated with increased utilization of any therapy included Asian race and Hispanic ethnicity. Among patients who received first‐line infusional therapy, factors associated with decreased utilization of second‐line infusional therapy included age, Medicaid eligibility, nonadenocarcinoma histology, and comorbidity; Asian race was associated with increased utilization of second‐line infusional therapy. Conclusion United States Food and Drug Administration (FDA) approvals of immunotherapy for the second‐line treatment of advanced NSCLC in 2015 were associated with increased rates of any second‐line treatment, but disparities based on social determinants of health persisted., United States Food and Drug Administration (FDA) approvals of immunotherapy for the second‐line treatment of advanced non‐small cell lung cancer in 2015 were associated with increased rates of any second‐line treatment in the Medicare population. However, disparities in immunotherapy uptake based on social determinants of health persisted, driven largely by differences in rates of any first‐line treatment.

Many cancer patients experience high symptom burden. Healthcare in the USA is reactive, not proactive, and doctor-patient communication is often suboptimal. As a result, symptomatic patients may suffer between clinic visits. In research settings, systematic assessment of electronic patient-reported outcomes (ePROs), coupled with clinical responses to severe symptoms, has eased this symptom burden, improved health-related quality of life, reduced acute care needs, and extended survival. Implementing ePRO-based symptom management programs in routine care is challenging. To study methods to overcome the implementation gap and improve symptom control for cancer patients, the National Cancer Institute created the Cancer-Moonshot funded Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium.Symptom Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) is one of three research centers that make up the IMPACT Consortium. SIMPRO, a multi-disciplinary team of investigators from six US health systems, seeks to develop, test, and integrate an electronic symptom management program (eSyM) for medical oncology and surgery patients into the Epic electronic health record (EHR) system and associated patient portal. eSyM supports real-time symptom tracking for patients, automated clinician alerts for severe symptoms, and specialized reports to facilitate population management. To rigorously evaluate its impact, eSyM is deployed through a pragmatic stepped wedge cluster-randomized trial. The primary study outcome is the occurrence of an emergency department treat-and-release event within 30 days of starting chemotherapy or being discharged following surgery. Secondary outcomes include hospitalization rates, chemotherapy use (time to initiation and duration of therapy), and patient quality of life and satisfaction. As a type II hybrid effectiveness-implementation study, facilitators and barriers to implementation are assessed throughout the project.Creating and deploying eSyM requires collaboration between dozens of staff across diverse health systems, dedicated engagement of patient advocates, and robust support from Epic. This trial will evaluate eSyM in routine care settings across academic and community-based healthcare systems serving patients in rural and metropolitan locations. This trial's pragmatic design will promote generalizable results about the uptake, acceptability, and impact of an EHR-integrated, ePRO-based symptom management program.ClinicalTrials.gov NCT03850912 . Registered on February 22, 2019. Last updated on November 9, 2021.

Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I–III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihood of developing new distant metastases.

PURPOSE The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative is a multi-institution effort to build a pan-cancer repository of genomic and clinical data curated from the electronic health record. For the research community to be confident that data extracted from electronic health record text are reliable, transparency of the approach used to ensure data quality is essential. MATERIALS AND METHODS Four institutions participating in AACR's Project GENIE created an observational cohort of patients with cancer for whom tumor molecular profiling data, therapeutic exposures, and treatment outcomes are available and will be shared publicly with the research community. A comprehensive approach to quality assurance included assessments of (1) feasibility of the curation model through pressure test cases; (2) accuracy through programmatic queries and comparison with source data; and (3) reproducibility via double curation and code review. RESULTS Assessments of feasibility resulted in critical modifications to the curation directives. Queries and comparison with source data identified errors that were rectified via data correction and curator retraining. Assessment of intercurator reliability indicated a reliable curation model. CONCLUSION The transparent quality assurance processes for the GENIE BPC data ensure that the data can be used for analyses that support clinical decision making and advances in precision oncology.

Importance Real-world data sets that combine clinical and genomic data may be subject to left truncation (when potential study participants are not included because they have already passed the milestone of interest at the time of study recruitment). The lapse between diagnosis and molecular testing can present analytic challenges and threaten the validity and interpretation of survival analyses. Observations Effects of ignoring left truncation when estimating overall survival are illustrated using data from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC), and a straightforward risk-set adjustment approach is described. Ignoring left truncation results in overestimation of overall survival: unadjusted median survival estimates from diagnosis among patients with stage IV non-small cell lung cancer or stage IV colorectal cancer were overestimated by more than 1 year. Conclusions and relevance Clinicogenomic data are a valuable resource for evaluation of real-world cancer outcomes and should be analyzed using appropriate methods to maximize their potential. Analysts must become adept at application of appropriate statistical methods to ensure valid, meaningful, and generalizable research findings.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

The immune checkpoint inhibitor (ICI) pembrolizumab is US FDA approved for treatment of solid tumors with high tumor mutational burden (TMB-high; ≥10 variants/Mb). However, the extent to which TMB-high generalizes as an accurate biomarker in diverse patient populations is largely unknown. Using two clinical cohorts, we investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing in solid tumors. TMB estimates from tumor-only panels substantially overclassified individuals into the clinically important TMB-high group due to germline contamination, and this bias was particularly pronounced in patients with Asian/African ancestry. Among patients with non-small cell lung cancer treated with ICIs, those misclassified as TMB-high from tumor-only panels did not associate with improved outcomes. TMB-high was significantly associated with improved outcomes only in European ancestries and merits validation in non-European ancestry populations. Ancestry-aware tumor-only TMB calibration and ancestry-diverse biomarker studies are critical to ensure that existing disparities are not exacerbated in precision medicine.

Importance Contemporary observational cancer research requires associating genomic biomarkers with reproducible end points; overall survival (OS) is a key end point, but interpretation can be challenging when multiple lines of therapy and prolonged survival are common. Progression-free survival (PFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) are alternative end points, but their utility as surrogates for OS in real-world clinicogenomic data sets has not been well characterized. Objective To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set. Design, setting, and participants A retrospective cohort study was conducted of patients with non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) whose tumors were genotyped at 4 academic centers from January 1, 2014, to December 31, 2017, and who initiated systemic therapy for advanced disease. Patients were followed up through August 31, 2020 (NSCLC), and October 31, 2020 (CRC). Statistical analyses were conducted on January 5, 2021. Exposures Candidate surrogate end points included TTD; TTNT; PFS based on imaging reports only; PFS based on medical oncologist ascertainment only; PFS based on either imaging or medical oncologist ascertainment, whichever came first; and PFS defined by a requirement that both imaging and medical oncologist ascertainment have indicated progression. Main outcomes and measures The primary outcome was the correlation between candidate surrogate end points and OS. Results There were 1161 patients with NSCLC (648 women [55.8%]; mean [SD] age, 63 [11] years) and 1150 with CRC (647 men [56.3%]; mean [SD] age, 54 [12] years) identified for analysis. Progression-free survival based on both imaging and medical oncologist documentation was most correlated with OS (NSCLC: ρ = 0.76; 95% CI, 0.73-0.79; CRC: ρ = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: ρ = 0.45; 95% CI, 0.40-0.50; CRC: ρ = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: ρ = 0.60; 0.55-0.64; CRC: ρ = 0.39; 95% CI, 0.32-0.46). Conclusions and relevance This cohort study suggests that PFS based on both a radiologist and a treating oncologist determining that a progression event has occurred was the surrogate end point most highly correlated with OS for analysis of observational clinicogenomic data.

PURPOSE Hospitalizations are a common occurrence during chemotherapy for advanced cancer. Validated risk stratification tools could facilitate proactive approaches for reducing hospitalizations by identifying at-risk patients. PATIENTS AND METHODS We assembled two retrospective cohorts of patients receiving chemotherapy for advanced nonhematologic cancer; cohorts were drawn from three integrated health plans of the Cancer Research Network. We used these cohorts to develop and validate logistic regression models estimating 30-day hospitalization risk after chemotherapy initiation. The development cohort included patients in two health plans from 2005 to 2013. The validation cohort included patients in a third health plan from 2007 to 2016. Candidate predictor variables were derived from clinical data in institutional data warehouses. Models were validated based on the C-statistic, positive predictive value, and negative predictive value. Positive predictive value and negative predictive value were calculated in reference to a prespecified risk threshold (hospitalization risk ≥ 18.0%). RESULTS There were 3,606 patients in the development cohort (median age, 63 years) and 634 evaluable patients in the validation cohort (median age, 64 years). Lung cancer was the most common diagnosis in both cohorts (26% and 31%, respectively). The selected risk stratification model included two variables: albumin and sodium. The model C-statistic in the validation cohort was 0.69 (95% CI, 0.62 to 0.75); 39% of patients were classified as high risk according to the prespecified threshold; 30-day hospitalization risk was 24.2% (95% CI, 19.9% to 32.0%) in the high-risk group and 8.7% (95% CI, 6.1% to 12.0%) in the low-risk group. CONCLUSION A model based on data elements routinely collected during cancer treatment can reliably identify patients at high risk for hospitalization after chemotherapy initiation. Additional research is necessary to determine whether this model can be deployed to prevent chemotherapy-related hospitalizations.

PURPOSE Large, generalizable real-world data can enhance traditional clinical trial results. The current study evaluates reliability, clinical relevance, and large-scale feasibility for a previously documented method with which to characterize cancer progression outcomes in advanced non–small-cell lung cancer from electronic health record (EHR) data. METHODS Patients who were diagnosed with advanced non–small-cell lung cancer between January 1, 2011, and February 28, 2018, with two or more EHR-documented visits and one or more systemic therapy line initiated were identified in Flatiron Health’s longitudinal EHR-derived database. After institutional review board approval, we retrospectively characterized real-world progression (rwP) dates, with a random duplicate sample to ascertain interabstractor agreement. We calculated real-world progression-free survival, real-world time to progression, real-world time to next treatment, and overall survival (OS) using the Kaplan-Meier method (index date was the date of first-line therapy initiation), and correlations between OS and other end points were assessed at the patient level (Spearman’s ρ). RESULTS Of 30,276 eligible patients,16,606 (55%) had one or more rwP event. Of these patients, 11,366 (68%) had subsequent death, treatment discontinuation, or new treatment initiation. Correlation of real-world progression-free survival with OS was moderate to high (Spearman’s ρ, 0.76; 95% CI, 0.75 to 0.77; evaluable patients, n = 20,020), and for real-world time to progression correlation with OS was lower (Spearman’s ρ, 0.69; 95% CI, 0.68 to 0.70; evaluable patients, n = 11,902). Interabstractor agreement on rwP occurrence was 0.94 (duplicate sample, n = 1,065) and on rwP date 0.85 (95% CI, 0.81 to 0.89; evaluable patients n = 358 [patients with two independent event captures within 30 days]). Median rwP abstraction time from individual EHRs was 18.0 minutes (interquartile range, 9.7 to 34.4 minutes). CONCLUSION We demonstrated that rwP-based end points correlate with OS, and that rwP curation from a large, contemporary EHR data set can be reliable, clinically relevant, and feasible on a large scale.

BACKGROUND/PURPOSE: Clinical trials in oncology evaluating the effects of patient reported outcomes (PRO) collection have found that monitoring of symptoms with PROs is associated with improved clinical care through reduced acute care utilization and decreased patient symptom burden. This educational review will evaluate strategies for systematic PRO integration into everyday oncology clinical practice. METHODS: We outline key considerations for using PROs in clinical practice, highlighting evidence from published studies. We also discuss the benefits and challenges of PRO implementation in oncology. RESULTS: Implementing PRO collection in clinical practice can improve care delivery and facilitate patient-centered clinical research. Considerations for using PROs in clinical practice include choice of instrument, method of delivery, and frequency of query. Challenges with implementing systematic PRO collection include the costs and resources needed for implementation, impact on clinical workflow, and controlling/monitoring physician burnout. DISCUSSION: While challenges exist in terms of financial resources and staff participation/burnout, patient reported outcomes in clinical practice provide a number of benefits including symptom monitoring, clinical research, and potential real-time personalized clinical decision support.

Patients with pre-existing autoimmune diseases have been excluded from clinical trials of immune checkpoint inhibitors (ICIs) for cancer. Real-world evidence is necessary to understand ICI safety in this population. Patients treated with ICIs from 2011 to 2017 were identified using data from a large health insurer. Outcomes included time to (1) any hospitalization; (2) any hospitalization with an irAE diagnosis; and (3) outpatient corticosteroid treatment. The key exposure was pre-existing autoimmune disease, ascertained within 12 months before starting ICI treatment, and defined either by strict criteria (one inpatient or two outpatient claims at least 30 days apart) or relaxed criteria only (any claim, without meeting strict criteria). Of 4438 ICI-treated patients, pre-existing autoimmune disease was present among 179 (4%) by strict criteria, and another 283 (6%) by relaxed criteria only. In multivariable models, pre-existing autoimmune disease by strict criteria was not associated with all-cause hospitalization (HR 1.27, 95% CI 0.998–1.62), but it was associated with hospitalization with an irAE diagnosis (HR 1.81, 95% CI 1.21–2.71) and with corticosteroid treatment (HR 1.93, 95% CI 1.35–2.76). Similarly, pre-existing autoimmune disease by relaxed criteria only was not associated with all-cause hospitalization (HR 1.11, 95% CI 0.91–1.34), but was associated with hospitalization with an irAE diagnosis (HR 1.46, 95% CI 1.06–2.01) and corticosteroid treatment (HR 1.46, 95% CI 1.13–1.88). Pre-existing autoimmune disease was not associated with time to any hospitalization after initiating ICI therapy, but it was associated with a modest increase in hospitalizations with irAE diagnoses and with corticosteroid treatment.

Objective The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies. Materials and Methods Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission. Results Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term. Discussion Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting. Conclusions Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative.

ImportanceMedicare’s Oncology Care Model (OCM) was an alternative payment model that tied performance-based payments to cost and quality goals for participating oncology practices. A major concern about the OCM regarded inclusion of high-cost cancer therapies, which could potentially disincentivize oncologists from prescribing novel therapies.ObjectiveTo examine whether oncologist participation in the OCM changed the likelihood that patients received novel therapies vs alternative treatments.Design, Setting, and ParticipantsThis cohort study of Surveillance, Epidemiology, and End Results (SEER) Program data and Medicare claims compared patient receipt of novel therapies for patients treated by oncologists participating vs not participating in the OCM in the period before (January 2015-June 2016) and after (July 2016-December 2018) OCM initiation. Participants included Medicare fee-for-service beneficiaries in SEER registries who were eligible to receive 1 of 10 novel cancer therapies that received US Food and Drug Administration approval in the 18 months before implementation of the OCM. The study excluded the Hawaii registry because complete data were not available at the time of the data request. Patients in the OCM vs non-OCM groups were matched on novel therapy cohort, outcome time period, and oncologist specialist status. Analysis was conducted between July 2021 and April 2022.ExposuresOncologist participation in the OCM.Main Outcomes and MeasuresPreplanned analyses evaluated patient receipt of 1 of 10 novel therapies vs alternative therapies specific to the patient’s cancer for the overall study sample and for racial subgroups.ResultsThe study included 2839 matched patients (760 in the OCM group and 2079 in the non-OCM group; median [IQR] age, 72.7 [68.3-77.6] years; 1591 women [56.0%]). Among patients in the non-OCM group, 33.2% received novel therapies before and 40.1% received novel therapies after the start of the OCM vs 39.9% and 50.3% of patients in the OCM group (adjusted difference-in-differences, 3.5 percentage points; 95% CI, −3.7 to 10.7 percentage points; P = .34). In subgroup analyses, second-line immunotherapy use in lung cancer was greater among patients in the OCM group vs non-OCM group (adjusted difference-in-differences, 17.4 percentage points; 95% CI, 4.8-30.0 percentage points; P = .007), but no differences were seen in other subgroups. Over the entire study period, patients with oncologists participating in the OCM were more likely to receive novel therapies than those with oncologists who were not participating (odds ratio, 1.47; 95% CI, 1.09-1.97; P = .01).Conclusions and RelevanceThis study found that participation in the OCM was not associated with oncologists’ prescribing novel therapies to Medicare beneficiaries with cancer. These findings suggest that OCM financial incentives did not decrease patient access to novel therapies.

Key Points Question Has the incorporation of checkpoint inhibitor immunotherapy into initial treatment of older Medicare-insured patients with advanced non–small cell lung cancer been associated with meaningful improvements in overall survival? Findings This cohort study included 19 529 patients s with Medicare coverage who initiated first systemic therapy for advanced lung cancer using 1 of 4 regimens of checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy. The median overall survival was 11.4 months among patients receiving pembrolizumab monotherapy and 12.9 months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, both substantially shorter than observed in registrational trials, with an adjusted restricted mean survival time through 18 months of follow-up of 11 to 12 months for all 4 treatment groups. Meaning In this study, immunotherapy among older Medicare-insured patients with advanced non–small cell lung cancer was associated with shorter overall survival than observed in key clinical trials, providing patients and physicians with estimates of outcomes for older patients who have lung cancer and are being treated with immunotherapy., Importance Immunotherapy is now a cornerstone of treatment for advanced non–small cell lung cancer (NSCLC), but its uptake and effectiveness among older patients outside clinical trials remain poorly understood. Objective To understand treatment patterns and evaluate the overall survival associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients who have advanced NSCLC and Medicare coverage. Design, Setting, and Participants This retrospective cohort study included Medicare-insured patients in the US aged 66 to 89 years who initiated first palliative-intent systemic therapy for lung cancer between January 1, 2016, and December 31, 2018. Survival follow-up continued through March 31, 2020. A total of 19 529 patients who had advanced lung cancer and were insured by a Medicare fee-for-service plan were included in the analysis. Exposures Regimens included pembrolizumab monotherapy (n = 3079), combined platinum-based drug (ie, cisplatin or carboplatin [hereinafter, platinum]) and pemetrexed disodium (n = 5159), combined platinum and a taxane (ie, paclitaxel, nab-paclitaxel, or docetaxel) (n = 9866), and combined platinum, pemetrexed, and pembrolizumab (n = 1425), as ascertained using Medicare claims from the Centers for Medicare & Medicaid Services. Main Outcomes and Measures The primary outcome was overall survival, which was measured using the restricted mean survival time (RMST) with propensity score adjustment for clinical and sociodemographic characteristics. Median survival was also reported for comparison with outcomes from registrational trials. Results A total of 19 529 patients (54% male, 46% female; median age, 73.8 [interquartile range, 69.9-78.4] years) were identified for analysis. The uptake of pembrolizumab-containing regimens in the Medicare population was rapid, increasing from 0.7% of first-line treatments in the second quarter of 2016 to 42.4% in the third quarter of 2018. Patients who were older (≥70 years, 2484 [81%]), were female (1577 [51%]), and/or had higher Risk Stratification Index scores (highest quintile, 922 [30%]) were more likely to receive single-agent pembrolizumab than chemotherapy. After propensity score adjustment, pembrolizumab was associated with survival similar to platinum/pemetrexed (RMST difference, −0.2 [95% CI, −0.5 to 0.2] months) or platinum/taxane (RMST difference, −0.7 [95% CI, −1.0 to −0.4] months). Patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy also had adjusted survival similar to those receiving platinum/pemetrexed chemotherapy (RMST difference, 0.5 [95% CI, 0.1-0.9] months). The unadjusted median survival was 11.4 (95% CI, 10.5-12.3) months among patients receiving single-agent pembrolizumab, approximately 15 months shorter than observed among pembrolizumab-treated participants in the KEYNOTE-024 trial. The unadjusted median survival was 12.9 (95% CI, 11.8-14.0) months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, approximately 10 months shorter than observed among platinum/pemetrexed/pembrolizumab–treated participants in the KEYNOTE-189 trial. Conclusions and Relevance Immunotherapy has been incorporated rapidly into treatment for patients with advanced NSCLC. However, survival estimates in the Medicare population are much shorter than those reported in registrational trials. These results provide contemporary estimates of survival for older patients with advanced NSCLC treated in routine practice, facilitating patient-centered decision-making., This cohort study assesses the treatment patterns of and survival outcomes associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients with advanced non–small cell lung cancer and Medicare coverage.

Objectives Patients with lung cancer have high symptom burden and diminished quality of life. Electronic patient-reported outcome (PRO) platforms deliver repeated longitudinal surveys via web or telephone to patients and alert clinicians about concerning symptoms. This study aims to determine feasibility of electronic PRO monitoring in lung cancer patients receiving treatment in community settings. Methods Adults receiving treatment for advanced or metastatic lung cancer at 26 community sites were invited to participate in a prospective trial of weekly electronic PRO symptom monitoring for 12 months (NCT03249090). Surveys assessing patients’ satisfaction with the electronic PRO system were administered at 3 months. Descriptive statistics were generated for demographics, survey completion rates, symptom occurrence, and provider PRO alert management approaches. Pairwise relationships between symptom items were evaluated using intra-individual repeated-measures correlation coefficients. Results Lung cancer patients (n = 118) participating in electronic PROs were older (mean 64.4 vs 61.9 years, p = 0.03), had worse performance status (p = 0.002), more comorbidities (p = 0.02), and less technology experience than patients with other cancers. Of delivered weekly PRO surveys over 12 months, 91% were completed. Nearly all (97%) patients reported concerning (i.e., severe or worsening) symptoms during participation, with 33% of surveys including concerning symptoms. Pain was the most frequent and longest lasting symptom and was associated with reduced activity level. More than half of alerts to clinicians for concerning symptoms led to intervention. The majority (87%) would recommend using electronic PRO monitoring to other lung cancer patients. Conclusions Remote longitudinal weekly monitoring of patients with lung cancer using validated electronic PRO surveys was feasible in a multicenter, community-based pragmatic study. A high symptom burden specific to lung cancer was detected and clinician outreach in response to alerts was frequent, suggesting electronic PROs may be a beneficial strategy for identifying actionable symptoms and allow opportunities to optimize well-being in this population.

Background Our study estimated insurance payments and patient out-of-pocket (OOP) expenses associated with discarded weight-based intravenous antineoplastic drugs for privately insured US adult patients with cancer. Methods We identified patients who received weight-based antineoplastic drugs from a 2017 MarketScan health risk assessment (IBM Corp, Armonk, NY) linked to claims data. Using weight information in the health risk assessment, we derived the recommended dose and calculated the percentage of drugs discarded. We applied β-regression to determine factors associated with the discarded percentages. To compare patients with and without high-deductible plans, we employed a generalized linear model and a 2-part model to examine insurance payment and OOP expense, respectively. All statistical tests were 2-sided. Results Of 27 350 claims for 58 weight-based antineoplastic drugs from 1970 patients, the median discarded percentage was 9.8% (mean [SD] = 12.8% [10.5%]). Aside from drug and tumor type, statistically significantly higher discarded percentages were found for patients in the lowest weight group (5.5% [95% confidence interval = 4.7% to 6.4%]; P Conclusions Private insurers incurred substantial financial burden from discarded weight-based antineoplastic drugs. Although the OOP expenses of discarded drugs were modest for most privately insured patients with cancer, approximately 5% spent more than $400 on the discarded drugs. Policies designed to reduce drug waste from single-dose, weight-based antineoplastic drugs should evaluate their financial consequences for payers and patients.

Purpose: We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor–positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification. Experimental Design: We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor–positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type. Results: A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR < 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group. Conclusions: ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group.

Background: Understanding the sources of variation in the use of high-cost technologies is important for developing effective strategies to control costs of care. Palliative radiation therapy (RT) is a discretionary treatment and its use may vary based on patient and clinician factors. Methods: Using data from the SEER-Medicare linked database, we identified patients diagnosed with metastatic lung, prostate, breast, and colorectal cancers in 2010 through 2015 who received RT, and the radiation oncologists who treated them. The costs of radiation services for each patient over a 90-day episode were calculated, and radiation oncologists were assigned to cost quintiles. The use of advanced technologies (eg, intensity-modulated radiation, stereotactic RT) and the number of RT treatments (eg, any site, bone only) were identified. Multivariable random-effects models were constructed to estimate the proportion of variation in the use of advanced technologies and extended fractionation (>10 fractions) that could be explained by patient fixed effects versus physician random effects. Results: We identified 37,361 patients with metastatic lung cancer, 3,684 with metastatic breast cancer, 5,323 with metastatic prostate cancer, and 8,726 with metastatic colorectal cancer, with 34%, 27%, 22%, and 9% receiving RT within the first year, respectively. The use of advanced technologies and extended fractionation was associated with higher costs of care. Compared with the patient case-mix, physician variation accounted for a larger proportion of the variation in the use of advanced technologies for palliative RT and the use of extended fractionation. Conclusions: Differences in radiation oncologists’ practice and choices, rather than differences in patient case-mix, accounted for a greater proportion of the variation in the use of advanced technologies and high-cost radiation services.

Background: Population-based metastatic recurrence rates for patients diagnosed with nonmetastatic colorectal cancer cannot be estimated directly from population-based cancer registries because recurrence information is not reported. We derived population-based colorectal cancer recurrence rates using disease-specific survival data based on our understanding of the colorectal cancer recurrence-death process. Methods: We used a statistical continuous-time multistate survival model to derive population-based annual colorectal cancer recurrence rates from 6 months to 10 years after colorectal cancer diagnosis using relative survival data from the Surveillance, Epidemiology, and End Results Program. The model was based on the assumption that, after 6 months of diagnosis, all colorectal cancer–related deaths occur only in patients who experience a metastatic recurrence first, and that the annual colorectal cancer–specific death rate among patients with recurrence was the same as in those diagnosed with de novo metastatic disease. We allowed recurrence rates to vary by post-diagnosis time, age, stage, and location for two diagnostic time periods. Results: In patients diagnosed in 1975–1984, annual recurrence rates 6 months to 5 years after diagnosis ranged from 0.054 to 0.060 in stage II colon cancer, 0.094 to 0.105 in stage II rectal cancer, and 0.146 to 0.177 in stage III colorectal cancer, depending on age. We found a statistically significant decrease in colorectal cancer recurrence among patients diagnosed in 1994–2003 compared with those diagnosed in 1975–1984 for 6 months to 5 years after diagnosis (hazard ratios between 0.43 and 0.70). Conclusions: We derived population-based annual recurrence rates for up to 10 years after diagnosis using relative survival data. Impact: Our estimates can be used in decision-analytic models to facilitate analyses of colorectal cancer interventions that are more generalizable.

An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal–Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication., The analysis of ctDNA obtained from low-volume blood samples has the potential to transform the management of patients with colorectal cancer. Nevertheless, research priorities and minimum standards for sample collection and analysis in this area are currently missing. In this Position Paper, the NCI Colon and Rectal–Anal Task Forces provide a set of recommendations designed to address these challenges and accelerate the implementation of ctDNA in the management of patients with colorectal cancer.

In just a few short weeks, the coronavirus disease 2019 (COVID-19) pandemic has transformed health care delivery around the globe. The crisis has dismantled how care is delivered and forced clinicians to make difficult triage decisions about what types and components of care have limited immediate value and which are essential for optimal outcomes. Because some malignancies could pose an immediate threat to survival, cancer provides a lens into the major shifts currently underway in clinical care. Cancer and cancer-related treatments frequently cause immunosuppression, and patients with cancer have excess mortality risk from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The magnitude of this risk is not yet known but early reports suggest a substantial increased risk of death associated with COVID-19 infection among patients with cancer, perhaps highest among those older than 60 years and those with pulmonary compromise.

IMPORTANCE: Patients 80 years and older with pancreatic ductal adenocarcinoma (PDAC) have not consistently received treatments that have established benefits in younger older adults (aged 60-79 years), yet patients 80 years and older are increasingly being offered surgery. Whether adjuvant chemotherapy (AC) provides additional benefit among patients 80 years and older with PDAC following surgery is not well understood. OBJECTIVE: To describe patterns of AC use in patients 80 years and older following surgical resection of PDAC and to compare overall survival between patients who received AC and those who did not. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study among patients 80 years or older diagnosed with PDAC (stage I-III) between 2004 to 2016 who underwent a pancreaticoduodenectomy at hospitals across the US reporting to the National Cancer Database. EXPOSURES: AC vs no AC 90 days following diagnosis of PDAC. MAIN OUTCOMES AND MEASURES: The proportion of patients who received AC was assessed over the study period. Overall survival was compared between patients who received AC and those who did not using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. A landmark analysis was performed to address immortal time bias. A propensity score analysis was performed to address indication bias. Subgroup analyses were conducted in node-negative, margin-negative, clinically complex, node-positive, and margin-positive cohorts. RESULTS: Between 2004 and 2016, 2569 patients 80 years and older (median [IQR] age, 82 [81-84] years; 1427 were women [55.5%]) underwent surgery for PDAC. Of these patients, 1217 (47.4%) received AC. Findings showed an 18.6% (95% CI, 8.0%-29.0%; P = .001) absolute increase in the use of AC among older adults who underwent a pancreaticoduodenectomy comparing rates in 2004 vs 2016. Receipt of AC was associated with a longer median survival (17.2 months; 95% CI, 16.1-19.0) compared with those who did not receive AC (12.7 months; 95% CI, 11.8-13.6). This association was consistent in propensity and subgroup analyses. In multivariable analysis, receipt of AC (hazard ratio [HR], 0.72; 95% CI, 0.65-0.79; P

Data are limited regarding whether the availability of biomarker-directed therapy for lung cancer exacerbates racial and socioeconomic disparities. Patients diagnosed with stage IV lung adenocarcinoma from 2008 to 2013 were identified using Surveillance, Epidemiology, and End Results Program-Medicare. The primary outcome was a Medicare claim for molecular testing within 60 days of diagnosis, analyzed using multivariable logistic regression; the secondary outcome was overall survival, analyzed using multivariable Cox proportional hazards models. All statistical tests were two-sided. Of 5556 patients, 1437 (25.9%) had molecular testing. Testing rates were 14.1% among black, 26.2% among white, and 32.8% among patients of Asian/other descent (adjusted P

The traditional approach to drug development in oncology, with discrete phases of clinical testing, is becoming untenable owing to expansion of the precision medicine paradigm, whereby patients are stratified into multiple subgroups according to the underlying cancer biology. Seamless approaches to drug development in oncology hold great promise of accelerating the accessibility of novel therapeutic agents to the public but are also accompanied by important trade-offs, including the limited availability of information on the clinical benefit and safety of novel agents at the time of market entry. In this Perspectives article, we describe several opportunities, in the form of novel trial designs or modelling strategies, to improve the efficiency of drug development in oncology, as well as new mechanisms to obtain information about anticancer therapies throughout their life cycle, such as innovative functional imaging techniques or the use of real-world clinical data.

Background Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes. Objectives This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality. Methods The study assembled a cohort from the Physicians’ Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age. Results Among 28,341 Physicians’ Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages. Conclusions HF is not associated with an increased risk of cancer among male physicians.

Background: Technological advances can improve care and outcomes but are a primary driver of health care spending growth. Understanding diffusion and use of new oncology therapies is important, given substantial increases in prices and spending on such treatments. Objectives: Examine diffusion of bevacizumab, a novel (in 2004) and high-priced biologic cancer therapy, among US oncology practices during 2005–2012 and assess variation in use across practices. Research Design: Population-based observational study. Setting: A total of 2329 US practices providing cancer chemotherapy. Participants: Random 20% sample of 236,304 Medicare fee-for-service beneficiaries aged above 65 years in 2004–2012 undergoing infused chemotherapy for cancer. Measures: Diffusion of bevacizumab (cumulative time to first use and 10% use) in practices, variation in use across practices overall and by higher versus lower-value use. We used hierarchical models with practice random effects to estimate the between-practice variation in the probability of receiving bevacizumab and to identify factors associated with use. Results: We observed relatively rapid diffusion of bevacizumab, particularly in independent practices and larger versus smaller practices. We observed substantial variation in use; the adjusted odds ratio (95% confidence interval) of bevacizumab use was 2.90 higher (2.73–3.08) for practices 1 SD above versus one standard deviation below the mean. Variation was less for higher-value [odds ratio=2.72 (2.56–2.89)] than lower-value uses [odds ratio=3.61 (3.21–4.06)]. Conclusions: Use of bevacizumab varied widely across oncology practices, particularly for lower-value indications. These findings suggest that interventions targeted to practices have potential for decreasing low-value use of high-cost cancer therapies.

Background Limited systematic data about complaints related to cancer care are available. Patient complaints related to ambulatory care at a large academic cancer center were examined to better understand patient experiences of care and prioritize opportunities for quality improvement. Methods Content analysis of outpatient complaints made to the Patient/Family Relations Office at Dana-Farber Cancer Institute, Boston, in a two-year period (January 2013–December 2014) were conducted. Narrative complaint records were reviewed independently by two to four reviewers to categorize primary and secondary reasons underlying complaints and to assess complaint severity. Results Among 78,668 outpatients seen during the two-year period, 266 complaints (0.3%) were made to the Patient/Family Relations Office. Some 48% of the complaints involved management issues, including finance and billing (10%), service issues (15%), delays (13%), and access and admission (6%); 11% of complaints related to quality and safety, whereas 41% of complaints related to relationships, including communication breakdowns (15%), patient-staff dialogue (5%), and humanness and caring (18%). Twenty percent of the complaints were classified as high severity, including 57% of quality- and safety-related complaints. Eleven percent of the patients involved in complaints ultimately transferred care to another provider or institution; 43% of high-severity complaints resulted in a transfer of care. Conclusion Most of the concerns represented in the complaints related to humanistic rather than technical aspects of care. A systematic review of complaints would offer the opportunity to improve patient-centeredness of care by identifying areas where care fails to meet patient and family needs.

Objective To compare alternative strategies for specifying cancer-free control cohorts for estimating cancer-attributable costs of care. Data Source, Study Design, Data Extraction Secondary data analysis of Surveillance, Epidemiology, and End Results data linked to Medicare claims among patients diagnosed with colorectal, lung, breast, and prostate cancers, 2007–2011. We estimated cancer-attributable costs using three alternative reference cohorts: (1) noncancer Medicare patients individually matched by demographic characteristics, (2) noncancer patients individually matched on demographic factors and comorbidity score, (3) cancer patients as their own control, using prediagnosis costs. Principal Findings Among 44,266 colorectal, 61,584 lung, 55,921 breast, and 67,733 prostate patients, mean total Medicare spending in the first year of diagnosis was $59,496, $54,261, $31,895, and $26,305, respectively. Estimates of cancer-attributable costs ranged from 79 percent to 82 percent of spending for colorectal, 76 percent–79 percent for lung, 65 percent–74 percent for breast, and 60 percent–75 percent for prostate cancers, depending on the reference cohort used. For all cancers, estimates were higher when patients were used as their own control, compared to demographic and comorbidity-matched controls. Conclusions Choice of reference group can have a substantial impact on proportion of total costs attributed to cancer and should be clearly defined in analyses of the costs of cancer care.

The AACR Project GENIE is an international data-sharing consortium focused on generating an evidence base for precision cancer medicine by integrating clinical-grade cancer genomic data with clinical outcome data for tens of thousands of cancer patients treated at multiple institutions worldwide. In conjunction with the first public data release from approximately 19,000 samples, we describe the goals, structure, and data standards of the consortium and report conclusions from high-level analysis of the initial phase of genomic data. We also provide examples of the clinical utility of GENIE data, such as an estimate of clinical actionability across multiple cancer types (>30%) and prediction of accrual rates to the NCI-MATCH trial that accurately reflect recently reported actual match rates. The GENIE database is expected to grow to >100,000 samples within 5 years and should serve as a powerful tool for precision cancer medicine. Significance: The AACR Project GENIE aims to catalyze sharing of integrated genomic and clinical datasets across multiple institutions worldwide, and thereby enable precision cancer medicine research, including the identification of novel therapeutic targets, design of biomarker-driven clinical trials, and identification of genomic determinants of response to therapy. Cancer Discov; 7(8); 818–31. ©2017 AACR. See related commentary by Litchfield et al., p. 796. This article is highlighted in the In This Issue feature, p. 783