bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of genetic testing results on patient-reported quality of life among patients undergoing panel testing for newly diagnosed ovarian cancer.
Authors: Lee Sarah S. , Frey Melissa Kristen , Gerber Deanna , Schwartz Zachary Phillip , Martineau Jessica , Lutz Kathleen , Reese Erin , Dalton Emily , Olsen Anne , Girdler Julia , Pothuri Bhavana , Boyd Leslie R. , Curtin John Patrick , Levine Douglas A. , Blank Stephanie V.
Published: May 2020

1584

Background: This study compared patient-reported stress, anxiety, and depression between newly diagnosed ovarian cancer patients with pathogenic genetic testing results versus patients with non-informative results (i.e., variants of uncertain significance (VUS) or negative). Methods: Patients underwent genetic testing (GT) via a facilitated referral pathway (Frey et al, Gynecol Oncol 2020) through which they were referred for genetic counseling and GT by their gynecologic oncologist within six weeks of diagnosis from 10/2015 to 5/2019. English-speaking patients completed three quality of life (QoL) instruments: Impact of Events Scale (IOES), State-Trait Anxiety Questionnaire (STAI), Hospital Anxiety and Depression Scale (HADS) immediately pre-and post-GT and 6 months post GT. Two-way mixed ANOVA was performed to analyze effect of GT results on QoL over time with significance p < 0.05. Results: One hundred ten patients were enrolled in the pathway and 83 (76%) patients underwent GT. Among these, 15 (18%) had potentially actionable pathogenic mutations ( BRCA1-8, BRCA2-4, MSH2-2, MRE11A-1); 26 (31%) had VUS results; 3 (4%) had both a pathogenic mutation and a VUS result; and 42 (51%) had negative results. Sixty patients (72%) completed QoL assessments pre and post GT, and 37 (44%) patients at 6-9 months post GT. For all patients, GT results did not affect QoL scales across our time points. By mean scores across all-comers, patients demonstrated mild stress at each time point and clinically significant anxiety immediate post-GT. All patients had a statistically significance decrease in HADS depression scores over time from pre-GT to 6 months post-GT (mean score 4.98 vs 2.97, p = 0.020). Patients with VUS had lower HADS mean anxiety scores across time (3.62) compared to patients with pathogenic (7.44) or negative mutations (6.83, p = 0.029). For patients without mutations, there was a significant decrease in clinically significant anxiety by STAI-state score at 6 months (p = 0.002) and a decrease in borderline anxiety by HADS scores at 6 months (p = 0.005). This effect was not present for patients with pathogenic mutations or VUS. Conclusions: A pathogenic result does not impact QoL scales immediately pre or post GT or at 6 months post GT, though patients with negative mutations were more likely to show a decrease in anxiety over time. Patients should be recommended GT at time of diagnosis of ovarian cancer without concern of increased stress, anxiety, or depression based on GT results.
Streamlining the genetics pipeline to increase testing for patients at risk for hereditary prostate cancer.
Authors: Tong Barry , Borno Hala , Small Eric Jay , Alagala Fern , Blanco Amie , Dhawan Mallika Sachdev
Published: May 2020

1590

Background: Metastatic prostate Cancer (mPCa) is increasingly recognized as a heritable disease and germline genetic testing has increasingly become a part of standard of care. At the University of California at San Francisco (UCSF) Genitourinary (GU) Medical Oncology clinic, approximately 850 new patients with mPCa are seen annually. A feasibility pilot Genetic Testing Station (GTS) was developed to expand access to genetic testing among this high-risk population. GTS is facilitated by Genetic Counselor Assistants (GCA) under the supervision of genetic counselors. Methods: This is a feasibility pilot of a GTS model among patients with mPCa. In this model, all patients with mPCa are offered a same day GTS visit with a GCA. At the GTS, the patient receives pre-test education via videos developed by genetic counselors. The patient provides informed consent, a family history, and a saliva sample for Invitae’s 87-gene panel. All positive results trigger a genetic counselor visit while non-positive results either receive a letter or a genetic counselor visit (in person or via telehealth). To evaluate the model, testing frequency and laboratory turnaround time (TAT) was assessed before and after the pilot. Results: In the first four months of the GTS pilot (10/14/2019 – 02/10/2020), 94 patients were referred and received genetic testing. Eight germline positives were identified (BRCA2, CHEK2, HOXB13 MSH6, RECQL4). The average TAT was 8 days. 9.3% of patients were found to have pathogenic mutations through the prostate GTS which is comparable to previously published rates of germline mutations in metastatic prostate cancer patients. In a 4-month time frame the prior to the intervention (10/01/2018-1/31/2019), 26 genetic testing orders were placed. The average laboratory TAT in this prior process was 17 days. Rates of positive germline mutations in the prior model was 8.6%. Conclusions: The GTS is a feasible method to increase access to germline genetic testing among a high-risk population. It may reduce barriers to testing and facilitate real-time discussion of treatment and prevention strategies with patients and family members. As a result, we will continue to operate the GTS. This model provides a framework for scaling access for and cascade testing in other high-risk patient groups.
Results of a prospective phase II national study: Prophylactic radical fimbriectomy (NCT01608074), in women with a documented high risk of breast/ovarian cancer—Final pathological results and outcomes.
Authors: Leblanc Eric , Narducci Fabrice , Hudry Delphine , Mailliez Audrey , Lemaire Anne-Sophie , Tresch-Bruneel Emmanuelle , Salzet Michel , Pomel Christophe , Caquant Frederic , Houvenaeghel Gilles , Charvolin Jean-Yves , Crouzet Agathe , Guyon Frederic , Fouche Yves , Ferron Gwenael , Gouy Sebastien , Vaini-Cowen Veronique , Fourchotte Virginie , Golfier Francois , Collinet Pierre
Published: May 2020

1594

Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard in surgical prophylaxis of pelvic high-grade serous carcinoma (HGSC) for women at risk of breast/ovarian cancer. Due to significant adverse effects of early oophorectomy, 20-30% of women delay or deny performing this operation. Recent data highlight the fallopian origin of most pelvic HGSC, especially its fimbrial part. Thus, we suggested a new two-step risk-reducing procedure: the radical fimbriectomy (RF) with delayed oophorectomy (DO) (Leblanc et al Gyn Oncol 2011), leading to the current RF/DO Phase 2 study. We present the definitive results on primary and secondary objectives of this trial. Methods: BRCA1/2 carriers or any women with a documented familial risk of breast/ovarian cancer were first counseled to perform a classical laparoscopic RRSO. If they denied, they were offered to enter the RF/DO study. All specimens were submitted to the SEE-FIM pathological protocol. Pathological data along with all intra- and 30-day and beyond post-operative adverse events were prospectively recorded. Follow-up consisted in an annual clinical breast and gynecological examination, with tumor markers and hormonal status assessment. Primary endpoint was the rate of pelvic serous carcinoma. Secondary endpoints were procedure morbidity, rates of tubal abnormalities, breast cancer, secondary oophorectomy. Results: From January 2012 to October 2014, 121 RF were performed: 120 by laparoscopy, 1 laparotomy (concurrent myomectomy). An occult neoplasia was found in 3 cases with 1 invasive HGSC. Intraoperative complications were two grade1 bleedings without transfusion with no grade ≥3 early post-operative or delayed complication. With a median follow-up of 5.3 years (0.2 -7.6), no patient developed any pelvic HGSC, 21 patients developed a breast cancer (3 de novo, 18 recurrences/contralateral.). 1 cancer-free BRCA1-mutated lady delivered safe twins, after an uneventful post-RF pregnancy obtained with assisted reproductive technology (ART). Overall, 29 women underwent DO (by choice: 12 or menopause: 17) resulting in grade 3b complication in 1 case, but no pathological abnormality. Conclusions: RF/DO appears as a safe, well tolerated and effective procedure in terms of occult neoplasia detection. A successful pregnancy with ART was possible after radical fimbriectomy. Longer follow-up and larger cohort are necessary to confirm its efficacy in terms of ovarian cancer prophylaxis. Clinical trial information: NCT01608074.
Multi-institutional comparative effectiveness of advanced cancer longitudinal imaging response evaluation methods: Current practice versus artificial intelligence-assisted.
Authors: Smith Andrew Dennis , Allen Brian C. , Abou Elkassem Asser , Mresh Rafah , Lirette Seth T. , Shrestha Yujan , Giese J. David , Stevens Reece , Williams Dillon , Farag Ahmed , Khalaf Ahmed ,   Society of Abdominal Radiology Emerging Technology Commission on Artificial Intelligence
Published: May 2020

2010

Background: Current-practice methods to evaluate advanced cancer longitudinal tumor response include manual measurements on digital medical images and dictation of text-based reports that are prone to errors, inefficient, and associated with low inter-observer agreement. The purpose of this study is to compare the effectiveness of advanced cancer longitudinal imaging response evaluation using current practice versus artificial intelligence (AI)-assisted methods. Methods: For this multi-institutional longitudinal retrospective study, body CT images from 120 consecutive patients with multiple serial imaging exams and advanced cancer treated with systemic therapy were independently evaluated by 24 radiologists using current-practice versus AI-assisted methods. For the current practice method, radiologists dictated text-based reports and separately categorized response (CR, PR, SD, and PD). For the AI-assisted method, custom software included AI algorithms for tumor measurement, target and non-target location labelling, and tumor localization at follow up. The AI-assisted software automatically categorized tumor response per RECIST 1.1 calculations and displayed longitudinal data in the form of a graph, table, and key images. All studies were read independently in triplicate for assessment of inter-observer agreement. Comparative effectiveness metrics included: major errors, time of image interpretation, and inter-observer agreement for final response category. Results: Major errors were found in 27.5% (99/360) for current-practice versus 0.3% (1/360) for AI-assisted methods (p < 0.001), corresponding to a 99% reduction in major errors. Average time of interpretation by radiologists was 18.7 min for current-practice versus 9.8 min for AI-assisted method (p < 0.001), with the AI-assisted method being nearly twice as fast. Total inter-observer agreement on final response categorization for radiologists was 52% (62/120) for current-practice versus 75% (90/120) for AI-assisted method (p < 0.001), corresponding to a 45% increase in total inter-observer agreement. Conclusion: In a large multi-institutional study, AI-assisted advanced cancer longitudinal imaging response evaluation significantly reduced major errors, was nearly twice as fast, and increased inter-observer agreement relative to the current-practice method, thereby establishing a new and improved standard of care.
Association between a national insurer’s pay-for-performance program for oncology and changes in prescribing of evidence-based cancer drugs and spending.
Authors: Bekelman Justin E. , Gupta Atul , Fishman Ezra , Debono David Joseph , Fisch Michael Jordan , Liu Ying , Sylwestrzak Gosia , Barron John , Navathe Amol S.
Published: May 2020

2016

Background: Efforts to standardize quality and control cost growth for cancer care have focused heavily on promoting evidence-based cancer drug prescribing. We evaluated the association between a national commercial insurer’s ongoing pay-for-performance (P4P) program for oncology and changes in prescribing of evidence-based cancer drugs and spending. Methods: Retrospective difference-in-differences quasi-experimental study utilizing administrative claims data from the insurer’s commercial health plans in 14 states covering 6.7% of US adults. We included patients 18 years of age or older with breast, colon, or lung cancer who were prescribed cancer drug regimens by 1,867 participating oncology physicians between 2013 and 2017. We leveraged the geographically staggered, time-varying rollout of the P4P program to simulate a stepped-wedge study design. Specifically, we estimated a patient-level model clustered by physician and used physician fixed-effects to examine pre- to post-intervention changes in evidence-based prescribing and spending for patients of participating physicians eligible earlier versus later in the period of P4P program rollout. We evaluated four categories of spending over a 6-month episode period: cancer drug spending; other (non-cancer drug) health care spending; total episode spending; and patient out-of-pocket spending. Results: The P4P program was associated with an increase in evidence-based regimen prescribing from 57.1% of patients in the pre-intervention periods to 62.2% in the post-intervention periods for a difference of +5.1 percentage points (pp) (95% CI 3.0 pp to 7.2 pp, P< 0.001). The P4P program was also associated with a differential $3,235 (95% CI $1,004 to $5,466, P= 0.005) increase in cancer drug spending, a differential $253 (95% CI $101 to $406, P= 0.001) increase in patient out-of-pocket spending, but no significant changes in other health care spending or total health care spending over the 6-month episode period. Conclusions: A national insurer’s oncology P4P program was associated with a 5.1 percentage point increase in prescribing of evidence-based cancer drug regimens. Our findings suggest that P4P programs may be effective in increasing evidence-based cancer drug prescribing at national scale -- enhancing cancer care quality. However, they may also increase out-of-pocket expenses and may not lead to savings in total health care spending during the 6-month episode.
Pilot program of remote monitoring for high-risk patients on antineoplastic treatment.
Authors: Daly Robert Michael , Kuperman Gilad , Zervoudakis Alice , Ro Alice , Roy Ankita , Baldwin Abigail , Salvaggio Rori , Holland Jessie C. , Chow Kimberly , Lauria Tara , Rozenshteyn Margarita , Zablocki Melissa , Chiu Yeneat Ophelia , Silva Nicholas , Perry Claire , Sokolowski Stefania , Wagner Isaac , Simon Brett A , Reidy Diane Lauren , Perchick Wendy
Published: May 2020

2027

Background: Early detection and management of symptoms in patients with cancer improves outcomes, however, the optimal approach to symptom monitoring and management is unknown. This pilot program uses a mobile health intervention to capture and make accessible symptom data for high-risk patients to mitigate symptom escalation. Methods: Patients initiating antineoplastic treatment at a Memorial Sloan Kettering regional location were eligible. A dedicated staff of RNs and nurse practitioners managed the patients remotely. The technology supporting the program included: 1) a predictive model that identified patients at high risk for a potentially preventable acute care visit; 2) a patient portal enabling daily ecological momentary assessments (EMA); 3) alerts for concerning symptoms; 4) an application that allowed staff to review and trend symptom data; and 5) a secure messaging platform to support communications and televisits between staff and patients. Feasibility and acceptability were evaluated through enrollment (goal ≥25% of new treatment starts) and response rates (completion of > 50% of daily symptom assessments); symptom alerts; perceived value based on qualitative interviews with patients and providers; and acute care usage. Results: Between October 15, 2018 and July 10, 2019, the pilot enrolled 100 high-risk patients with solid tumors and lymphoma initiating antineoplastic treatment (median age: 66 years, 45% female). This represented 29% of patients starting antineoplastics. Over six months of follow-up, the response rate to the daily assessments was 56% and 93% of patients generated a severe symptom alert (Table). Both patients and providers perceived value in the program and 5,010 symptom-related secure messages were shared between staff and enrolled patients during the follow-up period. There was a preliminary signal in acute care usage with a 17% decrease in ED visits compared to a cohort of high-risk unenrolled patients. Conclusions: This pilot program of intensive monitoring of high-risk patients is feasible and holds significant potential to improve patient care and decrease hospital resources. Future work should focus on the optimal cadence of EMAs, the workforce to support remote symptom management, and how best to return symptom data to patients and clinical teams. [Table: see text]
Nickel and dimed: Parking fees at NCI-designated cancer centers.
Authors: Lee Anna , Shah Kanan , Byun John , Chino Fumiko
Published: May 2020

2029

Background: Nonmedical costs from cancer treatment can be a significant out-of-pocket expense. As treatment may span over months, parking costs can become a significant burden on patients and caregivers. This cross-sectional study aims to report parking fees at National Cancer Institute (NCI)-designated cancer centers and to project parking costs for the treatment duration of certain cancers. Methods: Parking fees from NCI treatment centers were obtained via online search or phone call in Fall of 2019. City cost of living, median city household income, and discount availability were documented. Pearson correlation was used between parking costs and city variables. Parking costs were estimated for treatment of node positive breast cancer (12 daily rates plus 20 1-hr rates), definitive head and neck cancer (35 1-hr rates) and acute myeloid leukemia (AML) (42 daily rates). RStudio Version 1.2.5033 was used for analyses. Results: Parking costs were obtained for 100% of the 63 NCI centers included. Median city cost of living relative to New York City was 75.0 (out of 100); median city household income was $55,295 (range $28,974-$120,573). Twenty-five (40%) of NCI centers did not have detailed parking cost information online. Average parking costs were $3.55/hr (median $2, range 0-$15) and $7.79/day (median $5, range 0-$40). Twenty centers (32%) offered completely free parking for patients. Free parking was available at 43 (68%) centers for radiation appointments and 34 (54%) centers for chemotherapy appointments. Averaged estimated parking costs including discounts for a course of treatment for breast cancer was $122.03 (range 0-$800); head and neck cancer, $85.56 (range 0-$665); and AML hospitalization, $327.33 (range 0-$1470). City cost of living was positively correlated with daily parking costs (R = 0.7, p < 0.01) and negatively correlated with both free daily parking (R = -0.33, p = 0.02) and free parking during radiation (R = -0.34, p = 0.02) or chemotherapy (R = -0.37, p < 0.01). The median city household income was correlated with the daily parking costs (R = 0.30 p = 0.02) but not with free daily parking (R = -0.19, p = 0.16), free parking for patients on radiation (R = -0.23, p = 0.09) or on chemotherapy (R = -0.21, p = 0.14). Conclusions: Patients may face significant nonmedical costs through parking fees, even at centers that reflect the highest standard of care. There was high variability in costs with the potential for patients to pay hundreds of dollars in parking in order to receive their care. Efforts to minimize financial toxicity should focus on this potentially under-reported patient concern.
Identifying and overcoming clinical trial enrollment barriers: Can an integrated clinical pathways tool help bridge the gap?
Authors: McKinney Mishellene , Samborski Cynthia , Stefaniak Nessa , Murphy Monica L. , Edge Stephen B. , Attwood Kristopher , Liu Lu , Lash Stephen , Yu Wei , Eakle Katherine
Published: May 2020

2046

Background: Barriers to clinical trial (CT) enrollment continue to be a national challenge, with only about 3% of adult cancer patients treated within a CT. A key recommendation from the 2013 NCI-ASCO Cancer Trial Accrual Symposium was to use information technology to enhance identification of potentially eligible patients for CTs. We assessed if the implementation of a Clinical Oncology Pathways System (COP) with integrated CT information increased enrollment of CT’s, and categorized physician-identified reasons for non-enrollment. Methods: In 2018, Roswell Park Comprehensive Cancer Center (RP) implemented ClinicalPath pathways (formerly Via Oncology) for medical oncology. The COP software embeds interventional CTs that are open to accrual at RP in the pathway specific to a patient’s disease type, stage and biomarkers. The provider is presented with relevant CTs and must select screening for the trial or provide a reason for bypassing the CT from a drop-down list prior to being presented standard care options. CT screening requests from the COP system from 6/1/18-5/31/19 were reviewed. Screening requests and actual enrollment data were matched. The accrual-to-study ratio (ASR), defined as the number of consented accruals divided by the number of CTs open to accrual at RP at any time during the period, was calculated for the study period and the baseline from 6/1/14-6/1/18. The reasons physicians did not elect to screen for CTs were summarized. Results: There can be multiple trials presented for each pathway decision.There were 1,606 decision points with at least one embedded trial. Of these, 1,289 decision points matched 2,242 CTs that were not selected for screening. 317 trials were selected for screening. The most common reasons for not screening were patient ineligibility (41%), provider bypassing the CT by selecting treatment “off pathway” (28%), patient not interested (12%), patient already on CT (8%) and “other” (9%). Audits confirmed that the majority of ineligible patients had co-morbidities such as organ dysfunction or brain metastasis that precluded them from the CT. Among the 317 trials selected for CT screening, 108 (34%) patients enrolled in CTs. The ASR increased from the four-year historical average baseline of 4.08 to 4.33 one year post-implementation. Conclusions: The use of COP with embedded CT was associated with a modest increase in ASR. Stringent eligibility criteria was the primary barrier to enrollment. Adopting a broader set of clinical trial eligibility criteria could increase enrollment to CT.
Machine learning algorithms to predict financial toxicity associated with breast cancer treatment.
Authors: Sidey-Gibbons Chris , Asaad Malke , Pfob André , Boukovalas Stefanos , Lin Yu-Li , Offodile Anaeze
Published: May 2020

2047

Background: Financial burden caused by cancer treatment is associated with material loss, distress, and poorer outcomes. Financial resources exist to support patients but objective identification of individuals in need is difficult. Accurate predictions of an individual’s risk of financial toxicity prior to initiation of breast cancer treatment may facilitate informed clinical decision making, reduce financial burden, and improve patient outcomes. Methods: We retrospectively surveyed 611 patients who had undergone breast cancer therapy at MD Anderson Cancer Center to assess the financial impact of their care. All patients were over 18 and received either a lumpectomy or a mastectomy. We collected data using the FACT-COST patient-reported outcome measures alongside other financial indicators including income and insurance status. We extracted clinical and perioperative data from the electronic health record. Missing data were imputed using multiple imputation. We used this data to train and validate a neural network, LASSO-regularized linear model, and support vector machines. Data were randomly partitioned into training and validation samples (3:1 ratio). Analyses were informed by international PROBAST recommendations for developing multivariate predictors. We combined algorithms into a voting ensemble and assessed predictive performance using area under the receiver operating characteristics curve (AUROC), accuracy, sensitivity, and specificity. Results: In our validation sample, 48 of 203 (23.6%) women reported FACT-COST scores commensurate with significant financial burden. The algorithm predicted significant financial burden relating to cancer treatment with high accuracy (Accuracy = .83, AUROC = .82, sensitivity = .81, specificity = .82). Key clinical predictors of financial burden from linear models were neo-adjuvant therapy (βregularized 0.12) and autologous, rather than implant-based, reconstruction (βregularized 0.10). Conclusions: Machine learning models were able to accurately predict the occurrence of financial toxicity related to breast cancer treatment. These predictions may be used to inform decision making and care planning to avoid financial distress during cancer treatment or to enable targeted financial support for individuals. Further research is warranted to further improve this tool and assess applicability for other types of cancer.
Ranking of therapeutic regimens for hormone receptor-positive, HER2-negative, metastatic breast cancer (MBC) using information theoretic network meta-analysis.
Authors: Li Xuanyi , Tavana Hossein , Bhavnani Suresh , Warner Jeremy Lyle
Published: May 2020

2050

Background: Hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) is treated with targeted therapy, hormone therapy, chemotherapy, or combinations of these modalities. Evaluating the increasing number of treatment options is challenging, especially since few regimens have been compared head-to-head in randomized clinical trials (RCTs). Potential solutions include expert-driven guidelines (e.g. NCCN guidelines), algorithmic scales (e.g. the ASCO and ESMO Value Frameworks), traditional Bayesian network meta-analysis (NMA), and information theoretic (IT) NMA, a graph theory-based approach that also enables dynamic ranking of regimens over time. Methods: We used IT-NMA to rank regimens for HR+/HER2- MBC. The analysis includes RCTs of regimens identified from HemOnc.org and a recent large traditional NMA (Giuliano et al. 2019). Variables used in ranking include primary endpoints, no. of patients enrolled, p-value, hazard ratio for time-based outcomes (e.g. overall survival) or odds ratio for fixed endpoints (e.g. response rate), and year of publication. Results: The analysis included 238 RCTs enrolling 92,971 patients published between 1974-2019. There were 277 unique regimens, taking into account variations in dosage, frequency, and no. of cycles. As of 2019, out of 85 ranks, combinations of targeted therapy and hormone therapy (e.g. letrozole & palbociclib) are ranked the highest (Table). Over time, we observe that novel treatments tested in escalation trials tend to rise to the top of the rankings (e.g. paclitaxel & bevacizumab in 2007, driven by ECOG E2100), and monotherapy approaches tend to fall to the bottom. Conclusions: In 2019, the combinations of hormone or chemotherapy and targeted therapy are ranked higher than hormone therapy or chemotherapy alone. Our ranking result is similar to previous studies with a notably larger number of comparisons (Giuliano et al. is the largest published study, with 131 regimens/50,029 pts analyzed). Informatic theoretic NMA is a promising method of indirect rankings of treatment that also enables dynamic regimen ranking over time. [Table: see text]
Actionable policy barriers for receiving standard of care treatment among unresected stage III non-small cell lung cancer (NSCLC) patients in the United States.
Authors: Zheng Zhiyuan , Simone Charles B. , Chun Stephen G. , Han Xuesong , Sineshaw Helmneh M. , Zhao Jingxuan , Seal Brian S. , Yong Candice , Makari Doris , Rengan Ramesh
Published: May 2020

2069

Background: Recent data suggests that a significant number of good performance, unresectable stage III non-small cell lung cancer (NSCLC) patients do not receive standard-of-care treatment, i.e. concurrent chemoradiotherapy (cCRT) followed by durvalumab, despite being eligible. However, little is known about actionable policy barriers to delivery of cCRT to this patient population. Methods: The National Cancer Database (2004-2016) was used to identify unresected stage III NSCLC patients aged 18-79 years with Charlson comorbidity score ≤ 1. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 53,444) apart. The remaining treatment groups included sequential CRT (sCRT; n = 16,666), CT only (n = 15,416), RT only (n = 11,579), and no first course treatment (n = 16,691). Multinomial logistic regressions were used to examine the likelihoods of receiving different treatment modalities, controlling for patient demographics, Charlson comorbidity score, health insurance, facility type, social deprivation index (SDI, a comprehensive socio-economic measure; higher SDI indicates lower socioeconomic status [SES]), driving time to facility, diagnosis year, and region. Results: Of the total 113,796 patients assessed (median age 66 years), most were male (55.7%), non-Hispanic white (81.7%), and with SDI score ≥50 (51.3%). 29.5% had Charlson comorbidity score = 1 while the rest had 0. In adjusted analyses (predicted margins), 47.0% patients received cCRT (sCRT: 14.6%; CT only: 13.5%; RT only: 10.2%; no treatment: 14.7%). Compared to the privately insured, Medicaid, Medicare, and uninsured patients were more likely to receive RT only (relative risk ratios [95%CI]: 1.93 [1.77-2.11]; 1.51 [1.41-1.61]; 1.80 [1.61-2.01], respectively) and no treatment (1.84 [1.71-1.99]; 1.54 [1.45-1.63]; 2.19 [2.01-2.40], respectively) rather than cCRT (all p < .001). Moreover, higher SDI was associated with higher likelihood of receiving RT only (highest vs lowest SDI scores: 1.42 [1.33-1.52]), or no treatment (1.46 [1.38-1.55]) rather than cCRT (all p < .001). Longer driving time was associated with higher likelihood of receiving CT only ( > 120 mins vs < 30 mins: 1.24 [1.10-1.39]), or no treatment (1.33 [1.18-1.50]) rather than cCRT (all p < .001). Conclusions: Health policies should focus on patients who are not privately insured and live in neighborhoods with low SES. Moreover, helping their transportation needs may also improve the likelihood of receiving cCRT.
Opioid prescribing patterns among generalists & oncologists for Medicare Part D beneficiaries from 2013-2017.
Authors: Royce Trevor Joseph , Roberts Andrew , Dusetzina Stacie , Agarwal Ankit
Published: May 2020

2070

Background: In response to the opioid crisis, recent policies aiming to reduce opioid prescribing, misuse, & abuse have generated concern that patients with cancer pain may unintentionally experience reduced access to necessary opioid therapy. It is unknown how opioid prescribing patterns have changed between generalists and oncologists during this era. Methods: We conducted a longitudinal repeated cross-sectional study estimating adjusted annual national trends in opioid prescribing among generalists & oncologists using the Medicare Part D Prescriber Public Use Files 2013-2017. Poisson models estimated annual adjusted predicted mean rates of opioid prescribing-per-1,000 total prescriptions & long-acting opioid prescribing per-1,000 opioid prescriptions. Poisson models estimated adjusted incidence rate ratios (aIRRs) to quantify annual changes in prescribing rates. Results: From 2013-2017 the annual adjusted predicted mean rate of opioid prescriptions per 1,000 total prescriptions decreased from 53.4 to 41.3 among generalists (aIRR = 0.78; p < 0.01) and from 133.2 to 105.9 among oncologists (aIRR = 0.83; p < 0.01). The rate of long-acting opioid fills per 1,000 opioid prescriptions decreased from 96.0 to 87.0 (aIRR = 0.87; p < 0.01) and 235.1 to 222.5 (aIRR = 0.95; p < 0.01) for generalists & oncologists, respectively (Table). Conclusions: We found large declines in overall opioid prescribing rates among generalists (-22%) and oncologists (-17%) from 2013-2017. Long-acting opioid prescribing rates decreased over 2.5-times more among generalists than oncologists. Opioid policy & advocacy have been effective in reducing the extent of opioid prescribing in the Medicare population but how much of the decrease in prescribing by oncologists is ‘appropriate’ versus ‘inappropriate’ deserves further investigation. [Table: see text]
Mismatch between mortality burden and number of FDA registration trials in highly lethal cancers.
Authors: Gyawali Bishal , Yang Peter C. , Rubinstein Sam , Schoen Martin W. , Khaki Ali Raza , Warner Jeremy Lyle
Published: May 2020

2072

Background: Treatment successes in cancer are achieved through new drugs tested in clinical trials. However, drug discovery has been disparate across cancer types for various reasons. We sought to investigate if the number of trials used to support United States Food and Drug Administration (FDA) drug approvals is proportional to the incidence and mortality burden of highly lethal cancers, i.e. those with an expected relative mortality of >5% per Cancer Statistics, 2020 (Siegel et al.). Methods: All FDA labels for 258 antineoplastic cancer drugs approved as of January 2020 were reviewed for citations of registration trials supporting initial approval and additional indications. Trials were identified by matching described characteristics (e.g., patients enrolled, clinical trial NCT codes) to publications indexed on HemOnc.org. Trials were labeled by cancer type studied and type of trial (randomized vs non-randomized). Results: We identified 559 registration trials in total. Results for the six highly lethal cancers are shown in the table. The percent of registration trials was roughly proportional to incidence, but not mortality burden. For example, despite the 22% expected mortality burden of lung cancer, it had a share of only 11% of registration trials whereas breast cancer has an expected 7% mortality burden, with a share of 14% of registration trials. Chronic myeloid leukemia is expected to cause 1,130 deaths in 2020 (0.2%) and has had 20 registration trials (3.6%). The highly lethal cancers had a higher rate of randomized trials supporting approval than other cancers (84% vs 56%, p<0.001 [Chi-square]). Conclusions: While the findings may in part be due to disease biology (e.g., pancreatic ductal adenocarcinoma has proven resistant to many novel therapies), our evaluation highlights a potential mismatch between resources and needs. Randomized trials were more often used to support new drug approvals in highly lethal cancers. These findings will be important in regulatory policy. [Table: see text]
Resource and reimbursement barriers to comprehensive cancer care (CCC) delivery: An Association of Community Cancer Centers (ACCC) survey research analysis.
Authors: Benson Al Bowen , Boehmer Leigh , Shivakumar Latha , Trosman Julia Rachel , Weldon Christine B. , Hahn Elizabeth A. , Kircher Sheetal Mehta
Published: May 2020

2075

Background: CCC delivery is recommended in guidelines, required by accreditation bodies, and essential for high-quality cancer management. Barriers, such as insufficient reimbursement and lack of specialist staff, prevent consistent access to and delivery of CCC, particularly supportive oncology services. Challenges especially persist in community programs, where access to philanthropy and similar funding is limited. ACCC conducted a representative survey of its member programs to elucidate capacity and barriers to CCC delivery in the community/academic setting in order to inform policy and value-based payment reform. Methods: Survey development methodology included item generation with expert review, iterative piloting and cognitive interviews to achieve content and internal validity. An online survey was piloted at the ACCC 2018 Annual Meeting and sent to member programs via email link. The final survey included 22 questions on availability and funding for supportive services. Twenty-seven supportive oncology services were assessed for availability, reasons not offered, reimbursement/funding and patient payment. Analyses were conducted with SAS. Results: 172 of 704 ACCC member programs responded and completed the majority of survey as of 10/7/19. Despite a high proportion of programs offering supportive oncology services, gaps between cost and reimbursement were present for all (Table). Deficits in reimbursement are compensated by patient out-of-pocket payments, grants and donations. Most centers report needing more staffing in psychology (61%), social work (60%), navigation (59%), nutrition (57%), palliative care (56%), genetic counseling (52%), and financial counseling (53%). Gaps were observed regardless of region or practice type. Conclusions: There is a lack of sufficient reimbursement, staffing, and budget to provide CCC across the U.S., regardless of region or practice type. Oncology care models and reimbursement policies must include CCC services to optimize delivery of care. [Table: see text]
Documentation patterns and impact on observed side effects of the CANKADO ehealth application: An exploratory analysis of the PreCycle trial.
Authors: Degenhardt Tom , Harbeck Nadia , Fasching Peter A. , Wuerstlein Rachel , Lüftner Diana , Kates Ronald E. , Schumacher Johannes , Wenzel Claudia , Schinkoethe Timo , Schmidt Marcus
Published: May 2020

2083

Background: PreCycle (NCT03220178), a multicenter, randomized phase IV Intergroup trial evaluates the impact of ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer patients (pts) treated by palbociclib (P) and an aromatase inhibitor or P+fulvestrant. Pts willing to use the web/APP-eHealth solution CANKADO are eligible. Patients are randomized (2:1, stratified by therapy line) to the active (CANKADO PRO-React) or inactive inform arm. Primary endpoint is time to deterioration (TTD) of QoL. Methods: The trial started in 2017 and is ongoing (81 centers); regular safety reports are routinely provided to the study sponsor. Analysis of distribution of serious adverse events (SAE) was initiated by the trial leadership and performed using the Oct 15, 2019 safety report. Data that could bias primary or secondary endpoints were not analyzed. Bayesian inference (non-informative prior) was used to estimate probabilities; no corrections for potential multiplicities were made. Results: At data cut-off, 261/281 randomized patients had received study medication and provided CANKADO documentation. At time of evaluation, a total of 40298 days were documented. CANKADO was used on 59% (+/-10%) of all days over a 2-year period. SAEs were observed in 26/175 (14.9%) of all active-arm patients vs. 18/86 (20.9%) of inform-arm patients (90% probability of reduction in inform patients). Total SAEs were 36 (active) vs. 27 (inform); corresponding SAE incidence per hundred patients was 20.6 vs. 31.4, a relative reduction of about one-third. Conclusions: CANKADO is well accepted and used regularly by pts in PreCycle, so far over a 2-year period. The present (unplanned) analysis suggests a potentially substantial, clinically relevant reduction in relative SAE incidence among 1stL pts using PRO-React, with a more modest decrease overall. This analysis is preliminary, representing a snapshot, and cannot provide a definitive explanation for the observed SAE reduction. PreCycle will continue to enroll patients in order to further evaluate the potential benefits of interactive eHealth support. Collaborators: WSG WOMEN´S HEALTHCARE STUDY GROUP, CANKADO, Pfizer, AGO-TraFo, AGO-B, Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. Sponsor: Palleos Healthcare GmbH Keywords: eHealth, Adverse Events, Palbociclib Clinical trial information: NCT03220178.
The role of tumor markers for relapse detection in central nervous system non-germinomatous germ cell tumors (CNS-NGGCT): A pool analysis of cooperative group clinical trials.
Authors: Fonseca Adriana , Faure-Conter Cecile , Murray Matthew , Fangusaro Jason R. , Goldman Stewart , Bailey Shivani , Calaminus Gabriele , Khatua Soumen , Frappaz Didier , Dhall Girish , Nicholson James , Bouffet Eric , Bartels Ute Katharina
Published: May 2020

2503

Background: CNS-NGGCT are rare tumors that have been successfully treated with multimodal therapies. With a 5-yr EFS and OS of 72-84% and 82-93% respectively, surveillance and relapse detection is essential. Tumor marker (TM) elevation has proven to be a highly sensitive method of relapse detection in extra-cranial-NGGCT. We aim to determine the role of TM for relapse surveillance in children and adolescents with CNS-NGGCTs. Methods: European and North American data from germ cell tumor trials (SIOP GCT96, SFOP-TGM TC 90/92, COG-ACNS0122 and COG-ACNS1123) were pooled for analysis. Additionally, patients treated in the UK, Germany and France under strict protocol-guidelines were included. Details regarding imaging, pathology and TM elevation at diagnosis and relapse were collected. We report the proportion of relapses detectable by TM elevation. Results: Four-hundred and eighty-four patients enrolled in prospective cooperative group CNS-NGGCT trials from 1989 to 2016 were pooled for analysis. One-hundred and thirteen (23%) patients experienced a relapse/progression (SIOP GCT96: n = 57; SFOP TGM TC 90-92 n = 23, COG-ACNS0122 n = 16 & COG-ACNS1123 n = 17) and constitute the population of this report. Median age at diagnosis was 13 (range:1-30) years. The most common primary location was pineal in n = 60 (53%) patients. The site of relapse was available for 100 patients, 48 patients relapsed locally, 36 relapsed with distant disease, combined relapses were seen in 22 patients and 4 patients relapsed with TM elevation alone. TM in serum and/or CSF at diagnosis was available in 93(82%) patients, and in 90(80%) patients at the time of relapse. Eighty-four patients had TM available at both timepoints. At diagnosis 81 (96%) patients had TM elevation and 3 (4%) had negative TM. At relapse, 74(94%) patients with positive TM at diagnosis had TM elevation, while 7(6%) had TM negative. Conversely, 2/3 patients with negative TM at diagnosis, relapsed with elevated TM. Conclusions: Herein, we have assembled the largest prospective cohort to date of relapsed intracranial germ cell tumors. TM are highly sensitive detecting relapse/progression in CNS-NGGCT patients with elevated TM at diagnosis. The routine use of TM for relapse surveillance in patients with CNS-NGGCT can decrease the frequency of cross-sectional imaging, therefore, reducing lengthy hospital visits, sedation procedures and decreasing health-care costs.
Utilizing phenotypic characteristics of metastatic brain tumors to predict the probability of circulating tumor DNA detection from cerebrospinal fluid.
Authors: Li Meichen , Li Delan , Hou Xue , Zhang Xiangheng , Wang Na , Liang Jianzhong , Chen Jing , Wang Kaicheng , Wang Fufeng , Chen Yedan , Zhang Xian , Bao Hua , Wu Xue , Wang Xiaonan , Shao Yang , Chen Likun
Published: May 2020

2507

Background: Brain metastases occur in approximately 20% of tumor patients and is often associated with terminal events and poor prognosis. Cerebrospinal fluid (CSF) can be a promising source for detecting circulating tumor DNA (ctDNA) specific to the central nervous system (CNS) instead of peripheral blood due to the blood-brain barrier. However, CSF’s suboptimal ctDNA detection rate might limit its clinical application. Precise screening of suitable patients is needed to maximize clinical benefit. Methods: We sequenced 425 cancer-relevant genes in CSF and matched extracranial tissue or blood samples obtained from 67 lung cancer patients with brain metastases. The impact of clinical factors, including age, gender, tumor size, number of lesions, and distance of lesions to the ventricle on CSF ctDNA detection was then evaluated by univariate logistic regression. To predict the probability of successful CSF ctDNA detection, best subsets regression was employed for feature selection and cross validation was used for performance assessment to determine the final model. Results: We detected somatic alterations in 39/67 (58%) CSF ctDNA, 57/66 (86%) plasma ctDNA and 45/49 (92%) tissue samples. Mutation detection rate of CSF ctDNA was significantly lower than that from extracranial tissue and plasma (P < 0.001). Univariate analysis revealed significant association (P < 0.05) of high CSF ctDNA detection rate with the following features: (1) intracranial lesion size ( T), (2) shortest distance between the largest lesion and the ventricle ( Dtop), and (3) shortest distance between all intracranial lesion and the ventricle ( Dall). We also revealed a trend of higher detection rate in patients with CNS symptoms ( SCNS). Subsequent best subsets analysis and cross validation suggested best prediction power with lesion size and largest lesion-ventriclar distance (area under curve [AUC], 0.76 [95% CI, 0.71 to 0.85]; accuracy, 0.75 [95% CI, 0.70 to 0.81]). Final probability can then be derived from Logit P = 0.11×T−0.16×Dall (AUC, 0.82; sensitivity, 0.91; specificity, 0.74). The detection of CSF ctDNA was significantly improved from 58% to 83% (P = 0.03) based on the model. Conclusions: This study established a regression model to predict the probability of CSF ctDNA that can be useful to facilitate clinical decisions and avoid excessive practice when monitoring tumor evolution in the brain.
A prospective validation cohort study of baseline plasma cell-free DNA (cfDNA) as a prognostic biomarker in newly diagnosed glioblastoma (GBM).
Authors: Bagley Stephen Joseph , Nabavizadeh Seyed Ali , Till Jacob , Abdalla Aseel , Sanga Hareena , Mays Jazmine , Prior Timothy , Jurgielewicz Andrew , Guiry Samantha , Davtyan Karapet , Yee Stephanie S. , Binder Zev A , O'Rourke Donald M. , Brem Steven , Desai Arati Suvas , Carpenter Erica L.
Published: May 2020

2508

Background: Due to significant interpatient heterogeneity, survival outcomes vary widely in patients with GBM. Novel prognostic biomarkers are needed. We aimed to determine the prognostic impact of baseline plasma cfDNA concentration in patients with GBM. Methods: We analyzed 84 patients with newly diagnosed GBM and at least 7 months of follow-up time. The first 41 patients comprised a previously published derivation cohort (Bagley, Clin Cancer Res 2020). The subsequent 43 patients served as an independent validation cohort. cfDNA was extracted from plasma collected prior to initial surgical resection and quantified by qPCR for a 115 bp amplicon of the human ALU repeat element. Receiver operating characteristic (ROC) curve analysis was used in the derivation cohort to (1) assess the accuracy of plasma cfDNA concentration for predicting progression-free survival status at 7 months (PFS-7), a landmark based on the median PFS for newly diagnosed GBM (Stupp, N Engl J Med 2005), and (2) derive the optimal cutoff for dichotomizing patients into high- and low-cfDNA groups. In the validation cohort, logistic regression was used to measure the association of plasma cfDNA concentration (high vs. low) with PFS-7, adjusted for age, isocitrate dehydrogenase ( IDH) 1/2 mutational status, 0-6-methylguanine-methyltransferase ( MGMT) methylation, extent of resection, and performance status. Multivariate Cox regression was used for overall survival (OS) analysis. Results: In the derivation cohort, the optimal cutoff for plasma cfDNA was 25.0 ng/mL (area under the curve [AUC] = 0.663), with inferior PFS and OS in patients with cfDNA above this cutoff (PFS, median 4.9 vs. 9.5 months, log-rank p = 0.001; OS, median 8.5 vs. 15.5 months, log-rank p = 0.03). In the validation cohort, baseline plasma cfDNA concentration over the cutoff was independently associated with a lower likelihood of being alive and progression-free at 7 months (adjusted OR 0.13, 95% CI 0.02 – 0.75, p = 0.02). OS was also worse in in the validation cohort in patients with high plasma cfDNA (adjusted HR 3.0, 95% CI 1.1 – 8.0, p = 0.03). Conclusions: In patients with newly diagnosed GBM, high baseline plasma cfDNA concentration is associated with worse survival outcomes independent of other prognostic factors. Further validation in a larger, multicenter study is warranted.