Publications by authors named "Deborah Schrag"

311 Publications

Implementation of patient-reported outcomes for symptom management in oncology practice through the SIMPRO research consortium: a protocol for a pragmatic type II hybrid effectiveness-implementation multi-center cluster-randomized stepped wedge trial.

Trials 2022 Jun 16;23(1):506. Epub 2022 Jun 16.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: 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.

Methods: 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.

Discussion: 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.

Trial Registration: ClinicalTrials.gov NCT03850912 . Registered on February 22, 2019. Last updated on November 9, 2021.
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http://dx.doi.org/10.1186/s13063-022-06435-1DOI Listing
June 2022

Breast Medical Oncologists' Perspectives of Telemedicine for Breast Cancer Care: A Survey Study.

JCO Oncol Pract 2022 Jun 7:OP2200072. Epub 2022 Jun 7.

Dana Farber Cancer Institute.

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.
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http://dx.doi.org/10.1200/OP.22.00072DOI Listing
June 2022

Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial.

JAMA 2022 Jun 5. Epub 2022 Jun 5.

Mayo Clinic, Scottsdale, Arizona.

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.
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http://dx.doi.org/10.1001/jama.2022.9265DOI Listing
June 2022

Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials.

J Hematol Oncol 2022 May 21;15(1):69. Epub 2022 May 21.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs) monotherapy for the initial and long-term treatment of cancer-associated thrombosis (CAT). Several new randomized controlled trials (RCTs) have recently reported additional results on the safety and efficacy of DOACs in this setting. We performed an updated meta-analysis of all publicly available data from RCTs comparing DOACs with LMWHs for the treatment of CAT. Six RCTs enrolling 3690 patients with CAT were included. Compared with LMWHs, DOACs significantly decreased the risk of CAT recurrence (RR, 0.67; 95%CI, 0.52-0.85), with a non-significant increase in the risk of major bleeding (RR, 1.17; 95%CI, 0.82-1.67), a significant increase in the risk of clinically relevant nonmajor bleeding (RR 1.66; 95%CI, 1.31-2.09) and no difference in all-cause mortality rates. These results increase the level of certainty of available evidence supporting the use of DOACs as an effective and safe option for the treatment of CAT in selected cancer patients.
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http://dx.doi.org/10.1186/s13045-022-01289-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124390PMC
May 2022

Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial.

Oncologist 2022 Apr;27(4):292-298

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

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.
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http://dx.doi.org/10.1093/oncolo/oyab025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982431PMC
April 2022

CDX2 Biomarker Testing and Adjuvant Therapy for Stage II Colon Cancer: An Exploratory Cost-Effectiveness Analysis.

Value Health 2022 03 2;25(3):409-418. Epub 2021 Nov 2.

Division of Health Policy and Management, University of Minnesota School of Public Health, Minneapolis, MN, USA.

Objectives: 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.

Methods: 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.

Results: 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 of <0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jval.2021.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894795PMC
March 2022

A Scalable Quality Assurance Process for Curating Oncology Electronic Health Records: The Project GENIE Biopharma Collaborative Approach.

JCO Clin Cancer Inform 2022 02;6:e2100105

Memorial Sloan Kettering Cancer Center, New York, NY.

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.
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http://dx.doi.org/10.1200/CCI.21.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863125PMC
February 2022

Natural History and Characteristics of ERBB2-mutated Hormone Receptor-positive Metastatic Breast Cancer: A Multi-institutional Retrospective Case-control Study from AACR Project GENIE.

Clin Cancer Res 2022 May;28(10):2118-2130

Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.

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.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0885DOI Listing
May 2022

eSyM: An Electronic Health Record-Integrated Patient-Reported Outcomes-Based Cancer Symptom Management Program Used by Six Diverse Health Systems.

JCO Clin Cancer Inform 2022 01;6:e2100137

Memorial Sloan Kettering Cancer Center, New York, NY.

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.
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http://dx.doi.org/10.1200/CCI.21.00137DOI Listing
January 2022

Artificial intelligence-aided clinical annotation of a large multi-cancer genomic dataset.

Nat Commun 2021 12 15;12(1):7304. Epub 2021 Dec 15.

Memorial-Sloan Kettering Cancer Center, New York, USA.

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.
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http://dx.doi.org/10.1038/s41467-021-27358-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674229PMC
December 2021

Patterns of Adjuvant Chemotherapy Use and Association With Survival in Adults 80 Years and Older With Pancreatic Adenocarcinoma.

JAMA Oncol 2022 Jan;8(1):88-95

Division of Surgical Oncology, Department of Surgery, Dana-Farber Cancer Institute, Mass General Brigham, Boston, Massachusetts.

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 < .001), female sex (HR, 0.88; 95% CI, 0.80-0.96; P < .001), and surgery in the more recent time period (≥2011) (HR, 0.90; 95% CI, 0.82-0.99; P = .02) were associated with a decreased hazard of death. An increased hazard of death was associated with higher pathologic stage (stage II: HR, 1.68; 95% CI, 1.43-1.97; P < .001; stage III: HR, 2.39; 95% CI, 1.88-3.04; P < .001), positive surgical margins (HR, 1.49; 95% CI, 1.34-1.65; P < .001), length of stay greater than median (10 days) (HR, 1.17; 95% CI, 1.07-1.28; P < .001), and receipt of oncologic care at a nonacademic facilities (Community Cancer Program: HR, 1.20; 95% CI, 1.07-1.35; P < .001; Integrated Network Cancer Program: HR, 1.25; 95% CI, 1.07-1.46; P < .001).

Conclusions And Relevance: In this cohort study, the use of AC among patients who underwent resection for PDAC increased over the study period, yet it still was administered to fewer than 50% of patients. Receipt of AC was associated with a longer median survival.
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http://dx.doi.org/10.1001/jamaoncol.2021.5407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640950PMC
January 2022

Medicare Spending, Utilization, and Quality in the Oncology Care Model.

JAMA 2021 11;326(18):1805-1806

Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1001/jama.2021.18765DOI Listing
November 2021

Implications of Selection Bias Due to Delayed Study Entry in Clinical Genomic Studies.

JAMA Oncol 2022 Feb;8(2):287-291

Memorial Sloan Kettering Cancer Center, New York, New York.

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.
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http://dx.doi.org/10.1001/jamaoncol.2021.5153DOI Listing
February 2022

Electronic patient-reported outcomes monitoring during lung cancer chemotherapy: A nested cohort within the PRO-TECT pragmatic trial (AFT-39).

Lung Cancer 2021 12 30;162:1-8. Epub 2021 Sep 30.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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.
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http://dx.doi.org/10.1016/j.lungcan.2021.09.020DOI Listing
December 2021

Acute kidney injury in patients treated with immune checkpoint inhibitors.

J Immunother Cancer 2021 10;9(10)

Division of Hematology-Oncology, VAGLAHS, Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California, USA.

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.

Methods: We 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.

Results: ICPi-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.

Conclusions: Patients 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.
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http://dx.doi.org/10.1136/jitc-2021-003467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496384PMC
October 2021

Disparities in cancer prevalence, incidence, and mortality for incarcerated and formerly incarcerated patients: A scoping review.

Cancer Med 2021 10 3;10(20):7277-7288. Epub 2021 Sep 3.

Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

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.
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http://dx.doi.org/10.1002/cam4.4251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525139PMC
October 2021

Financial Burden of Discarded Weight-based Antineoplastic Drugs to Payers and Patients in the Private Insurance Market.

JNCI Cancer Spectr 2021 08 18;5(4). Epub 2021 May 18.

Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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%];  < .001; weight <150 lb [68.0 kg] vs ≥200 lb [90.7 kg]). Private payers spent $5090 per patient in 2017 on discarded weight-based antineoplastic drugs, and patients' mean OOP expense on discarded drugs was $63. In total, 39.7% of patients had high-deductible plans. The adjusted mean OOP expense for discarded drugs was statistically significantly higher for those in high-deductible plans ($95 vs $47;  < .001).

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.
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http://dx.doi.org/10.1093/jncics/pkab045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328094PMC
August 2021

Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non-Small Cell Lung or Colorectal Cancer.

JAMA Netw Open 2021 07 1;4(7):e2117547. Epub 2021 Jul 1.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.17547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314138PMC
July 2021

The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice.

Cancers (Basel) 2021 Jul 13;13(14). Epub 2021 Jul 13.

Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer "signal") and a cancer signal origin (i.e., tissue of origin). Participants with a "signal detected" will undergo further diagnostic evaluation per guiding physician discretion; those with a "signal not detected" will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a "signal detected" result is expected to be 106 (87-128). Subsequent diagnostic evaluation is expected to detect 52 (39-67) cancers. The positive predictive value of the MCED test is expected to be 49% (39-58%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.
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http://dx.doi.org/10.3390/cancers13143501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304888PMC
July 2021

A Review of the Diagnosis and Treatment of Metastatic Colorectal Cancer-Reply.

JAMA 2021 06;325(23):2405

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jama.2021.6027DOI Listing
June 2021

Clinical Inflection Point Detection on the Basis of EHR Data to Identify Clinical Trial-Ready Patients With Cancer.

JCO Clin Cancer Inform 2021 06;5:622-630

Division of Population Sciences, the Knowledge Systems Group, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

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.
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http://dx.doi.org/10.1200/CCI.20.00184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240790PMC
June 2021

Association Between First-Line Immune Checkpoint Inhibition and Survival for Medicare-Insured Patients With Advanced Non-Small Cell Lung Cancer.

JAMA Netw Open 2021 05 3;4(5):e2111113. Epub 2021 May 3.

Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.11113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140374PMC
May 2021

US Preventive Services Task Force Recommendations for Colorectal Cancer Screening: Forty-Five Is the New Fifty.

JAMA 2021 05;325(19):1943-1945

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jama.2021.4133DOI Listing
May 2021

Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma.

Cancer Discov 2021 10 29;11(10):2488-2505. Epub 2021 Apr 29.

Dana-Farber Brigham and Women's Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with p.H167_N173del. Expression of this EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic. SIGNIFICANCE: EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These EIDs are sensitive to FGFR inhibition , and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic..
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http://dx.doi.org/10.1158/2159-8290.CD-20-1669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8690974PMC
October 2021

Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review.

JAMA 2021 02;325(7):669-685

Division of Gastrointestinal Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.

Importance: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases.

Observations: Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor [EGFR]), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients.

Conclusions And Relevance: Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
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http://dx.doi.org/10.1001/jama.2021.0106DOI Listing
February 2021

Variation in Use of High-Cost Technologies for Palliative Radiation Therapy by Radiation Oncologists.

J Natl Compr Canc Netw 2021 04 12;19(4):421-431. Epub 2021 Feb 12.

2Division of Population Sciences and the Center for Outcomes and Policy Research, Dana-Farber Cancer Institute, Boston, Massachusetts.

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.
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http://dx.doi.org/10.6004/jnccn.2020.7633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109157PMC
April 2021

The impact of smoking on radical cystectomy complications increases in elderly patients.

Cancer 2021 05 22;127(9):1387-1394. Epub 2020 Dec 22.

Division of Urological Surgery, Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1002/cncr.33308DOI Listing
May 2021

Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Clin Trials 2021 02 1;18(1):104-114. Epub 2020 Dec 1.

Alliance Statistics and Data Center, Mayo Clinic, Scottsdale, AZ, USA.

Background: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested.

Methods: A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443).

Results: In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation.

Conclusion: A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.
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http://dx.doi.org/10.1177/1740774520975120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878323PMC
February 2021

Effect of High-Dose vs Standard-Dose Vitamin D Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.

Cancers (Basel) 2020 Nov 20;12(11). Epub 2020 Nov 20.

Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D (4000 IU) or standard-dose (400 IU) vitamin D. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D, high-dose vitamin D did not significantly change body weight [-0.7 kg; (95% CI: -3.5, 2.0)], body mass index [-0.2 kg/m; (95% CI: -1.2, 0.7)], muscle area [-1.7 cm; (95% CI: -9.6, 6.3)], muscle attenuation [-0.4 HU; (95% CI: -4.2, 3.2)], visceral adipose tissue area [-7.5 cm; (95% CI: -24.5, 9.6)], or subcutaneous adipose tissue area [-8.3 cm; (95% CI: -35.5, 18.9)] over the first 8 cycles of chemotherapy. Among patients with advanced or metastatic colorectal cancer, the addition of high-dose vitamin D, vs standard-dose vitamin D, to standard chemotherapy did not result in any changes in body composition.
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http://dx.doi.org/10.3390/cancers12113451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699725PMC
November 2020
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