bluuebunny/crossref_metadata_2025 huggingface dataset:
First data from OUT: The National Cancer Survey of LGBTQ+ survivors.
Authors: Scout Nfn , Veras Michelle ED , Rhoten Bethany Andrews , Lyerly Reece ED , Kasberg Aurea ED , Naimool Kk ED
Published: June 2021

e18544

Background: Cultural barriers that inhibit LGBTQ cancer care are a public health crisis. Although LGBTQ cultural competency trainings are rapidly becoming the norm, patient-centered information is lacking for healthcare professionals in cancer care. The purpose of OUT: The National Cancer Survey is to understand the experiences of LGBTQ cancer survivors in order to make cancer care a safer and more welcoming place for survivors and their support teams. Methods: Individuals age 18 or older currently living in the United States who have been previously diagnosed with cancer and who identify as LGBTQ+ were recruited via community partnerships and targeted paid social media advertisements with an oversample of media outreach to Black Indigenous and People of Color (BIPOC). Participants completed a cross-sectional web-based survey of their cancer care experiences. This resulted in a final sample of [1,600+] survivors, the largest known sample of LGBTQ+ cancer survivors in the world. The sample was weighted to adjust for U.S. sex assigned at birth and racial/ethnic demographics. Descriptive statistics were used to summarize participant responses, crosstabs were used to compare responses across demographic categories, and excerpted responses are used to highlight qualitative themes. Results: Participants ranged in age from X to X years (median X). X% of the sample identified as either gay or lesbian, X% as bi, and X% as trans or gender nonconforming. X% of the sample identified as White only, followed by X% as Latine, X% as Black and X% as other or mixed race. Most common cancer types included XYZ. When asked about welcoming care, X% of the sample reported they specifically sought an LGBTQ+ welcoming provider after diagnosis. Most common methods for finding such a provider included: X, X, and X. Most common cues that helped patients identify welcoming providers included X, X, and X. Overall X% reported receiving care in an LGBTQ+ welcoming environment but X% did not. Of those who did not receive care in a welcoming environment, they were more likely to be X, X, and X. Overall, X% of patients were out to their providers, but this varied by X, X, and X. The most common ways of coming out included X, X, and X. When asked what they wanted to tell health care providers to ensure better care, participants highlighted several themes, including: X, X, and X. These findings provide patient driven insights into how cancer care varies within the LGBTQ+ population by different demographic factors and specific strategies providers can take to enhance care for LGBTQ+ people.
Analysis of potential disparities in lung cancer clinical trial participation among Medicare beneficiaries.
Authors: Mishkin Grace E. , Franzini Luisa
Published: June 2021

e18548

Background: Disparities in clinical trial participation can mean disparities in medical advances, and disproportionate participation is an ethical issue even if differential results are not expected. The disparate impact of Covid-19 highlighted the importance of representativeness in trials aiming to prevent or treat disease. Previous analyses suggest there are likely significant differences in cancer clinical trial participants by race, ethnicity, and age. However, these analyses generally compare trial demographics to broad population demographics. Methods: This analysis used the SEER-Medicare linked database with claims data from 2014-2016 to compare lung cancer clinical trial participants to similar lung cancer patients not participating in a treatment trial. We compared the race, ethnicity, sex, age, and number of comorbidities for Medicare beneficiaries with at least one claim for an active treatment for lung cancer to the demographics of Medicare beneficiaries with at least one claim coded with the National Clinical Trials (NCT) number for an active treatment trial in lung cancer. The relationship between clinical trial participation and demographic variables was assessed using chi-square tests for binary variables and t-tests for continuous variables and corrected for multiplicity. A logistic regression model was used to assess robustness of these findings. Clinical trial participants were hypothesized to be more likely to be White, non-Hispanic, and male, and have a lower mean age and fewer comorbidities than the comparable non-trial active treatment population. Results: We compared 1,624 lung cancer clinical trial patients to 34,077 active treatment lung cancer patients. Clinical trial participants were more likely than non-trial active treatment patients to be female (53.6% vs. 50.4%, p = 0.015) or Asian/Pacific Islander (13.0% vs. 5.2%, p < 0.001) and less likely to be Black (5.2% vs. 9.0%, p < 0.001) or White (76.5% vs. 81.4%, p < 0.001). Trial participants had a lower mean age (70.7 vs. 73.7, p < 0.001) and fewer comorbidities (3.0 vs. 4.6, p < 0.001). There was not a significant difference by Hispanic ethnicity (5.2% vs. 4.4%, p = 0.106). The regression analyses supported these findings. Conclusions: Most analyses of clinical trials enrollment do not have a direct comparison group. Because this study is directly comparing lung cancer trial participants and non-participants from the same Medicare beneficiary population, the results fill a gap in our understanding of disparities in cancer clinical trial participation. Trial participants in this analysis were more representative than hypothesized, although the results supported previous findings that Black patients and older patients are underrepresented in cancer trials. There was also lower participation by White patients. Underrepresentation of patients with comorbidities may be due to trial eligibility criteria.
Review of cohort diversity in the development and validation of cancer risk assessment models.
Authors: Khan Ambreen , Amanda Gammon , Jeter Joanne M.
Published: June 2021

e18570

Background: Multiple validated models have been proposed to quantify an individual's lifetime risk of breast and colon cancer. However, an evaluation of the race and ethnicity of the cohorts studied in the development and validation of each of these models has not been reviewed. Predicting cancer risks accurately in Black, Indigenous and People of Color (BIPOC) can be crucial in helping to reduce cancer mortality rates and improving access to preventative care for these individuals. Methods: A literature search was conducted to identify published development and validation studies for the following cancer risk assessment models: Breast Cancer Surveillance Consortium (BCSC) Risk Calculator, Tyrer-Cuzick, Gail, Claus, CanRisk/BOADICEA, BRCAPRO and MMRPRO. Articles included were identified through review of a number of electronic databases and websites for the cancer risk prediction models. Authors were contacted for data not readily available through literature search. Results: A total of 15 development studies and 19 validation studies of the cancer risk prediction models were reviewed for the seven models listed above. Out of the 19 validation studies, seven were internal and twelve were external validation studies. 80% (12/15) of development studies and 68% (13/19) of validation studies did not include information on racial and ethnic composition of the cohorts. After obtaining additional information from authors, 53% (8/15) of the development studies were conducted solely in non-Hispanic White (NHW) cohort. The development cohorts ranged from 50%-100% NHW, 0%-7% non-Hispanic Black (NHB), 0%-8% Hispanic/Latinx, 0%-3% Asian and 0%-1% Indigenous participants. 58% (7/12) of external validation studies included ethnically and racially diverse populations compared to 14% (1/7) of internal validation studies. The BCBS, Gail, BRCAPRO and MMRPRO models were the only models with external validation studies conducted in ethnically or racially diverse populations. Overall, the model that had the most diverse cohort for its development and internal validation studies was the BCBS with 70% NHW, 6.7% NHB, 7.5% Hispanic/Latinx, 2.7% Asian, 0.8% Indigenous and 11.5% mixed/other ethnicities. Conclusions: The majority of the models reviewed did not have ethnically or racially diverse populations in their development and validation cohorts. Awareness of the under-representation of ethnically and racially diverse populations in these models is an important precaution for extrapolating data when using these models in medical decision making for BIPOC individuals. Although several barriers exist for participation of BIPOC individuals in clinical studies, these findings highlight the critical, yet unmet need for the development and use of appropriate cancer risk models in racially and ethnically diverse populations as a means to reduce health-related disparities.
Increasing underrepresented minority cancer patient enrollment into cancer clinical trials: A systematic review.
Authors: Nouvini Rosa , Parker Patricia A. , Malling Charlotte , Godwin Kendra , Costas-Muñiz Rosario
Published: June 2021

e18574

Background: Minorities continue to be underrepresented in clinical trials despite the National Institute of Health’s Revitalization Act, passed in 1993, mandating the representation of women and underrepresented minority groups in clinical trials. Studies have shown that although Blacks represent 15% and Hispanics 13% of the cancer population, their clinical trial enrollment rates in are disproportionately low at 4-6% and 3-6% respectively. We conducted a systematic review exploring interventions aimed at improving clinical trial enrollment for racial and ethnic minorities. Methods: A systematic search of PubMed, Cochrane CENTRAL, and Ovid PsycINFO was conducted for English-language studies of humans since 1993. Inclusion criteria included peer-reviewed, U.S.-based studies with interventions aimed to recruit underrepresented minority adult cancer patients into cancer clinical trials. We defined underrepresented minority groups as Black, Hispanic/Latino, Asian, American Indian/Alaska Native and Native Hawaiian/other Pacific Islander. Results: A total of 2471 titles and abstracts were identified and 2324 were excluded based on the eligibility criteria. A full text review was conducted of the remaining 147 articles, of which only 9 met criteria for our review. The interventions included patient navigation/coaching (n = 4), a clinical trial educational video (n = 2), institutional research infrastructure changes (n = 1), a relationship building and social marketing recruitment model (n = 1) and cultural competency training for providers (n = 1). Studies were conducted in a variety of practice settings including national cancer institutes and community practices. The quality of evidence was limited by the heterogeneity of study methods, patient representation and bias. Several studies had a homogeneous population of Black patients. Most studies (n = 7) were single arm trials that compared results to either historical controls or those cited in the existing literature; two studies were randomized controlled trials. A statistically significant improvement in accrual was shown in three of the patient navigation interventions, one of the clinical trial educational videos, the institutional research infrastructure change and the relationship building and social marketing recruitment model. The common threads to many of these successful interventions were support through the cancer care continuum, cultural congruency of research staff and culturally catered clinical trial educational materials. Conclusions: This systematic review illustrates several mechanisms by which to increase cancer clinical trial recruitment for cancer patients of underrepresented minority backgrounds in a variety of clinical settings. Randomized controlled trials with representation of multiple races/ethnicities are needed to further explore the benefits of these interventions.
Improving financial disclosures in oncology.
Authors: Heng Joseph , Polite Blase N.
Published: June 2021

e18642

Background: The Physician Payments Sunshine Act, as part of the Affordable Care Act, was enacted in 2010 to improve transparency of payments from drug and medical device manufacturers to physicians, which are easily accessible in a public database (OpenPayments CMS). However, in a review conducted of clinical drug trials in oncology, one-third of oncologist authors did not disclose their industry payments. Failure to disclose financial conflicts of interest can lead to a loss of public trust and in some cases may lead to legal liability. The American Society for Clinical Oncology and our institutional polices require all faculty to fully report financial conflicts of interest (COI). This pilot project aims to evaluate the accuracy of financial COI disclosures among our oncologists at the University of Chicago, and improve subsequent disclosures. Methods: This project was approved through the institutional quality improvement process. In May 2020, we crossmatched COI disclosures on journal publications for 37 practicing clinical hematologists/oncologists in our institution with 2017 and 2018 records on OpenPayments. We then conducted a department-wide Grand Rounds to review omissions, and to remind faculty of ASCO and University COI policies. In addition, we privately contacted individual oncologists to review any COI omissions. We reminded faculty that at the end of 2020 we would again review the accuracy of their disclosures. Results: We examined a total of 37 practicing hematologists/oncologists’ disclosure forms. At initial review, 6/37 (16.2%) of oncologists had incomplete or missing disclosures. A total of $569,182.95 in payments was not disclosed in 2018. 2 of these 6 oncologists did not disclose relevant payments from pharmaceutical companies whose drugs were referred to in publications. Several disclosure errors appeared to be inadvertent omissions as they were disclosed in other publications. Reasons given for disclosure omissions were: “oversight”, “did not believe to be relevant to publication”, “confusion over journal COI policies”, “unnecessary due to low payment amount”, "too many journals to update disclosures in". At the final review, only 2 of the 6 oncologists with disclosure omissions had updated disclosures at the end of the year despite education provided at multiple grand rounds and private communications. Conclusions: This pilot project demonstrated that education sessions and individual feedback improved adherence to COI disclosure policies, but not fully. Additional feedback and enforcement mechanisms may be required for full compliance. In addition, a centralized disclosure form (such as ASCO’s disclosure form) that journals can easily access may improve disclosure adherence.
Reduced blood product utilization via implementation of an anemia clinic and consult service in a large health system hospital.
Authors: Bowers Reid Christian , Korman Sandra Tomany , Thompson Michael A. , Sana Sherjeel , Pant Manish Krishna , Sanchez Federico Augusto
Published: June 2021

e18654

Background: An Anemia Clinic program was started Sept. 2016 as part of system wide implementation of Patient Blood Management (PBM) initiated in 2015. Methods: The Anemia Clinic accepted referrals for non-cancer anemia, predominantly preoperative cardiovascular surgery (CVS) Pts. Hgb thresholds were <13 g/dL in men and <12 g/dL in women. Non-anemia cytopenias triggered Hematology referral. All Pts were screened for iron, B12, folate, and reticulocyte. Nutrient deficiencies were supplemented. Pts with CKD or chronic disease were considered for erythropoiesis stimulating agents. Results: PBM implementation resulted in a drop in packed red blood cell (PRBC) usage (Table). Of CVS Pts pre-operatively anemic in 2020, 181 were referred to the Anemia Clinic and 259 were not. The percentage of Pts who received PRBCs after Anemia Clinic referral was not statistically different from those who were not referred (52.5% vs. 43.6% Chi-Square p=0.07). Of preoperatively anemic Pts who were transfused in 2020, an average of 1.49 PRBCs were used in the referred group vs. an average of 2.12 PRBCs in those in the not referred group (Poisson Means p=0.0009). Length of stay (LOS) which was a median 9d ( P25=6d, P75=16d) in the referred group vs a median 10d ( P25=6d, P75=16d) in the non-referred group was not statistically different between groups (Smirnov p=0.99). LOS analyses of observed-to-expected (O/E) ratios used the Premier Healthcare Providers Alliance Database (PHD) which contains data on approximately 45% of US hospital discharges. For 2020 through Nov. the referred group had an O/E = 0.89 (observed LOS μgeo = 9.97 days, expected LOS μgeo = 11.17 days, N=159). The not referred group had an O/E = 0.94 (observed LOS μgeo = 10.14 days, expected LOS μgeo = 10.83 days, N=232). Conclusions: PBM decreased PRBC use through systematization of best practices during the initial year. Subsequent addition of Anemia Clinic services did not decrease PRBC use further at first but appears to have contributed to this past year’s decrease. There is a trend toward shorter LOS for patients referred to Anemia Clinic but it is not statistically significant. Our methods improved nutrient deficiency identification which may improve both later health outcomes not detected here and access to treatment for hematologic malignancies.[Table: see text]
Impact of tobacco and illicit drug use in the care of adolescent and young adults with sarcoma.
Authors: Machhi Rushad , Parkes Amanda Marie
Published: June 2021

e18657

Background: Despite adolescent and young adults (AYAs) representing the patient population most likely to initiate and use tobacco and illicit drugs, studies of their impact have thus far focused on older cancer patients or those in survivorship. As sarcomas often serve as a model for AYA care and are associated with poor psychosocial function, frequent delays in diagnosis, and outcomes related to chemotherapy dose density, we sought to understand the impact of tobacco and illicit drug use on diagnosis, chemotherapy delays and dose reductions, and no-show rates in AYAs with sarcoma. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with sarcoma seen at least once in 2019 at the University of Wisconsin, identifying documentation of tobacco, marijuana, and other illicit drug use and comparing to pre-identified cancer outcomes including days from symptom onset to tissue diagnosis (with delay defined as > 120 days from symptoms to diagnosis), chemotherapy delays > 1 week and dose reductions, and appointment no-show rates. Current substance use was defined as use following cancer diagnosis. Results: We identified 46 AYAs with sarcoma, with documented tobacco use in 20% as current (9/46), 13% as former (6/46) and 67% as none (31/46). Marijuana and illicit drug use were less frequent at 17% (8/46) and 7% (3/46) respectively. Delayed diagnoses were more common in patients with current tobacco use (6/9, 67%) as compared with former or non-smokers (12/37, 32%, p = 0.12) and were seen in all patients with illicit drug use (3/3, 100%), as compared with only 35% without illicit drug use (15/43, p = 0.05). Of the 24 patients who received chemotherapy, chemotherapy delays and dose reductions were more common in current tobacco users at 86% (6/7) and 29% (2/7) respectively, as compared with patients with former or no tobacco use at 71% (12/17) and 18% (3/17) respectively. Chemotherapy dose reductions were also more common in patients with illicit drug use (2/3, 67%) versus no illicit drug use (3/21, 14%, p = 0.10). Appointment no-show rates were higher in current tobacco users versus former or non-smokers, with 44% (4/9) versus 27% (10/37) with a no-show rate > 5%. In patients with documented substance use, oncology providers documented 93% of tobacco use (14/15) but only 38% marijuana use (3/8) and 33% illicit drug use (1/3) and no oncology providers documented a cessation plan. Conclusions: Current tobacco and illicit drug use in AYAs with sarcoma were associated with delays in diagnosis, increased chemotherapy delays and dose reductions, and higher no-show rates, highlighting modifiable risk factors. Even more strikingly, oncology providers had low rates of documentation of marijuana and illicit drug use in AYAs and no documentation of plans for cessation, highlighting a lost opportunity and the need for more standardized substance use assessment and evidence-based cessation interventions for AYAs with cancer.
Quality indicators for glioblastoma treatment: An audit from a tertiary care cancer center in India.
Authors: Goyal Love , Chakraborty Santam , Saha Saheli , Roy Paromita , Zameer Lateef , Mishra Deepak , Parihar Mayur , Chandra Aditi , Arunsingh Moses , Chatterjee Sanjoy , Mallick Indranil , Bhattacharyya Tapesh , Biswas Bivas , Basu Achari Rimpa
Published: June 2021

e18659

Background: Surgery followed by chemoradiotherapy with temozolomide (TMZ) is the standard of care for glioblastoma. There are limited reports of quality metrics in glioblastoma. We present an audit of adherence to selected quality indicators proposed in the PRIME Quality Improvement study. Methods: Retrospective audit of quality indices for glioblastoma patients treated between 2017 - 2020. Patients were treated within a standard protocol of postsurgical integrated molecular diagnosis, radiotherapy with concurrent and adjuvant TMZ. Multiparametric MRI at predefined time-points of pre- and post radiation, interim and end of adjuvant TMZ guided management. Demographic, clinical, pathological, imaging, therapy and outcomes data was abstracted. Numbers with proportions for indices were calculated. Survival was estimated using the Kaplan Meier method. Results: Ninety-four glioblastoma patients were treated from 2017 to 2020. Quality metrics are reported (table). Patients in whom adjuvant TMZ could not be started or continued for 6 cycles had progressive disease and salvage chemotherapy was initiated. The 12 month overall and progression free survival was 74.6% (95% CI : 65.4% - 85.1%) and 43.6% (95% CI : 33.8% - 56.3%) respectively. Conclusions: Our patients met quality indices in most domains; outcomes are comparable with global results. These metrics will be periodically evaluated and updated to include newer standards to assess our continued service appropriateness.[Table: see text]
Real-world trends in biosimilar prescribing among oncology providers, 2019-2021.
Authors: McGlynn Kelly A. , McGarry Jacqueline , Patel Kashyap B. , Clinton Natasha
Published: June 2021

e18701

Background: The number of approved biosimilars in the United States has increased exponentially in recent years. Within the oncology market, there are currently 14 approved biosimilars, with 11 launched since the start of 2019. The emergence of new oncology biosimilars provides a tool for success in value-based care, and has the potential to lower costs to patients and providers and expand access to care. Methods: Analysis of biosimilar prescribing behavior was performed using 2020 prescription data (Wolters Kluwer, n = 130,836), sales data (IQVIA), and dosage data for patients taking bevacizumab, trastuzumab, rituximab, or an FDA-approved biosimilar for these products (FDA Purple Book), between 2019-2021 (ION Solutions, n = 69,884). Drugs not directly interchangeable with the bevacizumab, trastuzumab or rituximab reference products according to NCCN guidelines were excluded. Results: Biosimilar products are currently available for bevacizumab (2 biosimilars), rituximab (3 biosimilars), and trastuzumab (5 biosimilars). We found that in 2020, 8.2% of new prescriptions for any of these three reference products were for a biosimilar. An analysis of real-world drug administration data revealed that in the 3 months following the 2019 launch of trastuzumab’s first biosimilar (trastuzumab-anns), 7.3% of initiating line 1 patients were prescribed the biosimilar over the reference product. During the same period in 2020, when a total of 5 trastuzumab biosimilars were available, 80.5% of initiating line 1 trastuzumab patients began treatment on a biosimilar, suggesting rapid uptake by providers. However, this differed by product, with the initial uptake for the first rituximab biosimilar (rituximab-pvvr), at only 2.3%. Uptake also occurred within treatment lines, with 11.1% of all patients (bevacizumab: 11.3%, trastuzumab: 14.1%, rituximab: 7.9%) switching from a reference product to a biosimilar during treatment. Uptake was particularly rapid for trastuzumab biosimilars: among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to trastuzumab-anns in the first 90 days post-launch. Biosimilars launched at significantly lower prices than their reference products, with cost per prescription at -42.0%, -29.9% and -89.5% relative to the reference product for trastuzumab, rituximab and bevacizumab, respectively. However, biosimilar launches had little impact on reference product pricing, with 2019-2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all three reference products. Conclusions: We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.
Clinical relevance of comprehensive genomic profiling for advanced cancers in India.
Authors: Elizabeth Joseph Serena , Mathew Aju , Rajappa Senthill J. , Rohatgi Nitesh , Sirohi Bhawna , Jain Reetu , Agarwala Vivek , Shukla Deepak Kumar , Mehta Anurag , Pramanik Raja , Talwar Vineet , Maka Vinayak , Raut Nirmal Vivek
Published: June 2021

e18718

Background: Comprehensive genomic profiling (CGP) assay, a next-generation sequencing (NGS) based technique generates a large amount of genomic information about a cancer. While CGP is increasingly used in low-middle income countries (LMIC), little is known about the extent to which these benefits patients. Here we describe the proportion of patients with advanced cancer in India who eventually receive targeted therapy for an actionable genetic alteration identified on CGP assays. Methods: This was a multicenter, retrospective cohort study in adult patients with advanced non-hematological malignancies who underwent a CGP test. We excluded patients who were identified to have a genetic alteration that has a well-validated targeted standard-of-care therapy (e.g.; EGFR exon 18, 19, 21 mutations for lung cancer, HER2 amplification for breast cancer). Participating oncologists provided anonymized information of consecutive CGP test reports through an online data capture form. Descriptive statistics were used to describe the proportion of patients with subsequent targeted therapy. Results: During 2019-20, 12 medical oncologists provided CGP reports for 297 patients; 235 met the inclusion criteria. Fourteen different testing panels were used by the oncologists. Among the study cohort, 45% were male. Eighty nine percent underwent tumor tissue biopsy and 11% had liquid biopsy. The most common cancers were lung (19%), breast (18%), pancreatobiliary (9%) and colorectal (6%). Patients received a median of 2 lines (range: 0-5) of prior systemic therapy. Based on the CGP assay, 35 patients (15%) received targeted therapy. Among them, 29% was for HER2 amplification (non-breast cancer), 26% for PIK3CA mutation, 11% for HER2 or EGFR exon 20 insertion mutation (lung cancer), 5% each for BRAF mutation (non-melanoma), EGFR mutation (non-lung cancer) and MET mutation. Conclusions: In a LMIC setting, 15% patients received a targeted therapy based on CGP assay. This is comparable to reports from high income countries. Considering the limited access to new drugs and clinical trials, this finding requires further analysis.
Seminomatous and non-seminomatous mediastinal germ cell tumors (MGCT): A real-world analysis from two tertiary care centers in India.
Authors: Sharma Aparna , Biswas Bivas , Reddy Rohit , Thumbudorai Robin , Ganguly Sandip , Dabkara Deepak , Pramanik Raja , Kumar Sunil , Sahoo Ranjit Kumar , Sharma Atul , Kumar Lalit , Batra Atul
Published: June 2021

e18726

Background: Mediastinal germ cell tumor (MGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We describe the real-world treatment patterns and outcomes of MGCT treated at two tertiary care centres in India. Methods: Patients diagnosed with GCT (any site) at two large tertiary care centres from January 2010 to December 2020 in India were identified using the ICD-09 code (C-62) from prospectively kept databases. From these databases, a manual search was performed to identify MGCT patients. A chart review was done to retrieve demographic, tumor-related (serum tumor marker levels as per International germ cell cancer consensus (IGCCC)) and treatment details. Relapse free survival (RFS) and overall survival (OS) were estimated and compared for seminomatous and non-seminomatous MGCT. Results: A total of 54 patients were identified and all were males with a median age of 25 years (interquartile range, 18-45). Common presenting symptoms included cough (81.4%) shortness of breath (64.8%), chest pain (25.9%), superior vena cava obstruction (20.3%), pleural effusion (18.5%) and pericardial effusion (5.6%). Approximately one-thirds (n = 17) were seminomatous, while two-thirds were non-seminomatous (n = 37). Serum tumors markers levels were S0 (7.4%),S1 (42.6%),S2 (29.6%) and S3 (20.4%). Treatment was primarily by multiagent chemotherapy [ Bleomycin/Etoposide/cisplatin(BEP) 63.0%, EP (Etoposide/Cisplatin) 18.5%, VIP (etoposide/ifosfamide/cisplatin) 13.0%). Median number of cycles administered was 3 (Range 1-6). Three patients did not receive chemotherapy (all seminoma) and were treated with upfront surgery. In total, 11 patients (20.4%) underwent surgery, and eight (14.8%) received radiation. Three patients were not evaluable for response, 33.3% achieved complete response (CR),44.4% achieved partial response (PR), 9.3% had SD (stable disease) and 7.4% progressed on first line chemotherapy. Median follow up was 14.4 months (95% confidence interval [CI] 9.03 -26.16). Three year relapse free survival was 64.0% in overall population, and 100% in seminoma vs 41.5% in non-seminoma (P < 0.001). Three year OS was 80.2% in all patients and 94.1% for seminoma versus 70.0% in non-seminoma (P = 0.178). Conclusions: In this largest real-world analysis of MGCT, we found excellent long-term survival rates for patients with seminomatous MGCT, while further optimization of treatment is needed for those with non-seminomatous MGCT.
Costs, throughput time, and proportion of valid test results, a model-based analysis of liquid biopsies for stage IV non-small cell lung cancer.
Authors: Koole Simone N. , Schouten Robert , Vessies Daan , Schuurbiers Milou , Bosch Linda J.W. , van den Heuvel Michel , van Harten Wim , van den Broek Daan , Monkhorst Kim , Retel Valesca P.
Published: June 2021

e18844

Background: Tissue diagnostics for metastasized non-small cell lung cancer (NSCLC) is hampered by the difficulty of obtaining tissue biopsies, and sequential testing. This leads to patient burden, and a time-consuming diagnostic trajectory, sometimes without valid test results. We analyzed the diagnostic process of liquid biopsies (ctDNA) as an addition to tissue diagnostics, for patients with stage IV NSCLC. Methods: Data was retrieved from stage IV patients (N=209) included in the observational, Lung cancer Early Molecular Assessment trial (LEMA; NCT02894853). Within this study, plasma and tissue was collected upfront. Sequencing of ctDNA was performed retrospectively, and compared to results from tissue diagnostics, as performed in the including hospital, including test results, success-rates, and identified targets per patient. Throughput time for tissue, and costs for diagnostics were calculated within a single specialized institute. Because of the retrospective nature of the ctDNA assessment, diagnostics for implementation of ctDNA was modelled (1 run per week), based on estimations for the trajectory and throughput time. A discrete-event simulation model was developed with three scenarios: 1) diagnostics with tissue biopsy alone (comparator); 2) diagnostics with ctDNA first, and tissue biopsy if required; 3) ctDNA if biopsy failed. The process scope ranged from tissue/blood retrieval to outcome in terms of targets. Simulation analysis was performed, calculating mean price per patient (pp), median throughput time pp, and targets found per scenario. Results: In scenario 1, 85% of the patients had a clinically relevant test result, compared to 93% and 92% when ctDNA was added in scenario 2 and 3, respectively. Scenario 2 was the fastest, but also the costliest scenario: median throughput time 15 days pp (IQR 8-30) and mean costs of €2.716 pp (standard deviation [SD] €789) (Table). In this scenario, 9.9% of the biopsies could be cancelled, and in 39.6% a simple biopsy with immunohistochemistry was sufficient. Conclusions: The addition of ctDNA may lead to better informed treatment decisions in patients with stage IV NSCLC. Discrete-event simulation analysis showed that the addition of ctDNA in the diagnostic process increased proportion of patients with a clinically relevant test-result in both scenarios. Throughput time is faster, and additional costs per patient are limited, especially when ctDNA is added after biopsy failure. Clinical trial information: NCT02894853. [Table: see text]
Event free survival in adults with relapsed ALL who underwent front-line therapy with CALGB 10403.
Authors: Raychaudhuri Suravi , Yurkiewicz Ilana , Mannis Gabriel N. , Medeiros Bruno C. , Coutre Steve E. , Muffly Lori S. , Liedtke Michaela
Published: June 2021

e19005

Background: CALGB 10403 is a pediatric-inspired ALL regimen that has recently been shown to have improved survival rates in adolescents and young adults with ALL when compared to historical outcomes with traditional adult ALL regimens (Stock et. al, 2019). Methods: This is a retrospective cohort study of ALL patients who received induction CALGB 10403 at Stanford University (both on and off trial), achieved CR1, and subsequently relapsed. Primary outcome of interest was event free survival from time of diagnosis. Events were defined as relapse or death. Secondary outcomes were overall survival and event free survival from first relapse. Patients were censored at time of last clinical follow up. Results: 25 patients met inclusion criteria and received front-line CALGB 10403 from April 2010 to September 2018. At the time of initial diagnosis median age was 30 years (range 18 – 39 years). 68% of patients were male. 48% of patients were overweight and 40% were obese. 76% of patients had precursor B cell ALL while 24% had T cell ALL. 12% had CNS disease at diagnosis. 36% of patients had WBC greater than 30k. 12% of patients had CRLF2 rearrangement. 12% of patients were MRD positive after first induction. 20% of patients received rituximab. Median event free survival time from diagnosis was 20 months (range 3 – 79 months) and median overall survival time was 53 months. Blinatumomab was the most common salvage therapy after 1st relapse, followed by inotuzumab. 15 patients (60%) achieved CR2, of which 4 (27%) were MRD positive after 2nd induction. 15 patients (60%) went to HSCT. Of the patients who achieved CR2, 8 relapsed for a second time. Median event free survival time after first relapse was 23 months. Survival 1 year after relapse was 60%. 11 of the 25 patients were alive at last follow up. Median follow up time of survivors was 6 years. Conclusions: This is a descriptive retrospective cohort study of adult patients in a real world setting who received CALGB 10403 induction and subsequently relapsed. Compared to other studies of relapsed ALL patients who were induced with traditional chemotherapy (Fielding et. al, 2007), survival 1 year after relapse was much higher (60% vs. 22%). As CALGB 10403 becomes an increasingly common induction regimen for AYA and adults with ALL, further outcomes study is required.[Table: see text]
Improved transfusion independence rates for momelotinib versus ruxolitinib in anemic JAKi naïve myelofibrosis patients independent of baseline platelet or transfusion status.
Authors: Kiladjian Jean-Jacques , Platzbecker Uwe , Mayer Jiří , Illés Árpád , Prejzner Witold , Woźny Tomasz , Tzvetkov Nikolay , Vannucchi Alessandro M. , Kirgner Ilya , Nagy Zsolt , Grosicki Sebastian , Derolf Åsa , Lazaroiu Mihaela Cornelia , Yoon Sung-Soo , Goh Yeow Tee , von Bubnoff Nikolas , Verstovsek Srdan , Klencke Barbara J. , Donahue Rafe , Mesa Ruben A.
Published: June 2021

e19039

Background: Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of JAKi naïve or previously JAKi treated intermediate/high risk MF patients as demonstrated in the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 was conducted in JAKi-naïve patients with MF (n = 432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX). MMB demonstrated a statistically non-inferior splenic response rate (SRR) to RUX at the W24 landmark analysis in S1 but did not meet significance for total symptom score (TSS) response. Low SRR and TSS response was observed for RUX in patients with low platelets, while MMB elicited consistent SRR and TSS response across the platelet subsets, comparable to the response in the ITT. Transfusion independence (TI) at W24 was higher for MMB vs RUX patients across all PLT strata. Methods: Progressive anemia is a common occurrence in MF with nearly all MF patients requiring transfusions as their disease advances. Given the prognostic importance of Hgb and transfusion status in MF patients including evidence that achieving or maintaining transfusion independence by Week 24 with momelotinib is associated with improved OS in S1 and S2, we expanded the previously reported retrospective platelet subset analysis to explore the W24 TI response rates for MMB and RUX randomized patients in S1 by baseline Hgb and PLT levels and transfusion status. Results: The data presented here suggest that the prognostically-important W24 TI rate was substantively higher in anemic patients receiving MMB versus RUX, irrespective of the degree of anemia. MMB is also more effective relative to RUX in achieving or maintaining TI in JAKi naïve patients irrespective of baseline PLT count or baseline transfusion status. Conclusions: Together with data suggesting that TI response at W24 with momelotinib is associated with a survival advantage, these data further support the potential TI benefits of inhibiting ACVR1 in addition to JAK1 and JAK2 with MMB in MF patients. Clinical trial information: NCT01969838, NCT02101268. [Table: see text]
Pulmonary fungal infections in acute leukemias and aggressive lymphomas: Analysis of the United States National Inpatient Database.
Authors: Ozoya Oluwatobi , Ayuk Adaeze , Lawal Odunayo , Emole Josephine
Published: June 2021

e19042

Background: For patients undergoing intensive chemotherapy, pulmonary fungal infections (PFI) represent a major cause of morbidity and mortality. Our study examined predictors and outcomes of PFI in hospitalized patients (pts) with hematological malignancies in the current era of antifungal prophylaxis for high-risk patients. Methods: Using the 2018 National Inpatient Sample (NIS) database, we conducted a retrospective study of hospitalized pts aged ≥ 18 years, with acute leukemias or aggressive lymphomas. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes for leukemias, lymphomas and PFI (candidiasis, aspergillosis, cryptococcus, and mucormycosis). Demographics, comorbidities, and outcomes were compared between pts with and without PFI using Chi-squared test. Multivariable logistic regression was performed to explore predictors associated with PFI. Results: Of 205,525 hospitalizations that met the inclusion criteria, PFI was diagnosed in 1635 (0.8%). Frequent infections were aspergillosis (80%) and candidiasis (11%). Pts with acute myeloid leukemia (AML) accounted for 64% of all PFI. The PFI group, compared to non-PFI, were more likely to be non-Caucasian (39% vs 32%, p<0.05), have higher Charlson comorbidity index (CI) [64% vs 55%, p<0.01], longer mean length of stay (23 vs 9 days, p<0.001), and more likely to have AML (64% vs 33%, p<0.001). Pts with PFI had higher odds of acute respiratory failure, severe sepsis, and in-hospital mortality. Mortality rates for PFI and non-PFI group were 17% and 6% respectively (p<0.001). Predictors associated with PFI were Hispanic or Native American race, Charlson CI ≥ 3, neutropenia, malnutrition, bone marrow transplant status and diagnosis of AML (Table). Conclusions: Our study identified clinical variables that predicted for PFI in patients with acute leukemias and aggressive lymphomas. Pts with these high-risk characteristics should get priority for close surveillance, mold-specific prophylaxis, and antifungal therapeutic drug monitoring. Selected predictors associated with pulmonary fungal infections. Adjusted Odds ratio (OR).[Table: see text]
Trichostatin A sensitivity signature across hematological cell lines.
Authors: Przychodzen Bartlomiej
Published: June 2021

e19521

Background: Histone deacetylase inhibitors (HDACi) are small molecules that increase acetylation of lysine residues by blocking histone deactylases. These anticancer agents affect epigenetic and non-epigenetic gene expression resulting in cell cycle arrest of cancer cells. Furthermore HDACi can enhance its anti-tumor effects via the pharmacologic modulation of macrophage. Some HDACi’s such as Trichostatin A (TSA) can also affected the tumor immune microenvironment by suppressing the activity of infiltrating macrophages and inhibiting myeloid-derived suppressor cell recruiement (Li et al.,). Methods: We conducted a high throughput screen comparing gene expression profiles in known hematological cell lines to identify transcriptional signatures associated with TSA sensitivity obtained from GDSC. Results: We selected genes that showed at least 2fold expression difference and were statistically significant (p < 0.05). We identified 49 genes that were upregulated and 85 that were downregulated. The most significant results include multiple genes known to be correlated with the B-cell maturation process. We found that CD24 a small GPI linked glycoprotein expressed at the surface of most B lymphocyte precursors, neutrophils, epithelial cells and frequently found to be highly expressed in various hematological and solid neoplasms, was up/downregulatred by XX. Interestingly, CD24 plays a role in the activation and differentiation of the cells as bone marrow samples lacking CD24 resulted in decreased numbers of both pre-B and immature B-cell populations. We also found that IKZF2, a transcription factor regulating lymphocyte development and queiesence and which is frequently deleted in hypodiploid B-ALLs. This result could revelent as other reports suggest a role of IKZF2 as a tumor suppressor with a central role regulating the balance of self-renewal and differentiation in leukemic stem cells. Conclusions: Our study identified transcriptional profiles which suggest that TSA sensitivity could be related to B cell maturation. Further experiments warrant replication of these findings which could prove useful in creating optimal, TSA-based treatments acting either as potent single agents or in combination enhancing anti-tumor effects of immunotherapies.
Healthcare utilization and costs associated with first-line treatment with obinutuzumab- and rituximab-based regimens for follicular lymphoma.
Authors: Ta Jamie T. , To Tu My , Sud Cheryl , Shapouri Sheila , Seetasith Arpamas
Published: June 2021

e19536

Background: Current real-world data on healthcare utilization (HCU) and costs of common first-line (1L) follicular lymphoma (FL) regimens, including obinutuzumab (G), remain limited. The aim of this study was to examine real-world HCU and costs for the most common National Comprehensive Cancer Network (NCCN)-recommended 1L FL treatments. Methods: This was a retrospective cohort study using administrative claims data from the IQVIA PharMetrics Plus and IBM MarketScan Commercial and Medicare Supplemental databases. We identified patients (pts) ≥18 years, who had ≥1 inpatient claim or ≥2 outpatient claims, with a diagnosis of FL from February 1, 2015 to March 31, 2020, and had received 1L FL treatment (per NCCN guidelines) between February 1, 2016 and September 30, 2019. The first claim for FL treatment was the index date. All pts had ≥12 months of pre- and ≥6 months of post-index continuous enrollment in medical and pharmacy benefits. Pts with other primary cancers, FL treatment, or stem cell transplant during the pre-index period, and clinical trial participation or end-stage renal disease during the study period were excluded. All-cause HCU and costs (2020 USD) per pt during the 6-month post-index period were reported for the five most common 1L FL regimens (only complete NCCN regimens were considered). Results: Overall, 1991 pts met the eligibility criteria, and 53% were male. The mean (standard deviation [SD]) age and Charlson Comorbidity Index at index were 58 (10.4) years, and 1.7 (1.0), respectively. The most common 1L regimens were rituximab-bendamustine (R-benda; n=818 [41.1%]), R-monotherapy (R-mono; n=592 [29.7%]), R-CHOP (n=461 [23.2%]), G-benda (n=86 [4.3%]), and R-CVP (n=34 [1.7%]). The proportion of pts who had ≥1 hospitalization or an emergency room visit was highest with R-CHOP (26.7% and 33.6%, respectively) and lowest with R-mono (11.3% and 18.1%, respectively). Mean (SD) all-cause total healthcare costs were highest with R-benda and G-benda, followed by R-CHOP, R-CVP, and R-mono (Table). Mean (SD) all-cause medical and FL treatment costs (drug and administration) were highest for R-benda ($174,407 [$110,520]; $135,520 [$96,492]) and lowest for R-mono ($87,368 [$83,910]; $54,271 [$40,433]). Conclusions: This real-world study provides an update on HCU and costs among pts initiating current NCCN-recommended 1L treatment for FL. Unadjusted 6-month total healthcare costs were highest with R-benda, followed by G-benda, while the lowest costs were seen with R-CVP and R-mono. Future studies with adjustment for pt characteristics are needed to compare HCU and costs between FL regimens.[Table: see text]