bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast cancer survivorship and level of institutional involvement utilizing integrative oncology.
Authors: Crudup Terri , Li Linna , Dorr Jennifer Wright , Lawson Elizabeth , Stout Rachel , Niknam Pedram Vazifeh , Jones Judi , Steen Robert , Lu Lynn L , Casner Susan , Wang Yi , Scott James , Zanine Shelby , Robertshaw Stacey , Broderick Gabriella , Singh Simarpreet , Lu Jingsong , Zhou Li , Palommella Vaishali , Jonas Wayne
Published: June 2021

e18588

Background: A growing body of evidence has shown that a Whole Person Integrative Oncology approach, adding the use of complementary and lifestyle therapies to cancer treatments, benefits patients by improving patient-reported outcomes and potentially extending overall survival. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in Integrative Oncology at the institutions treating those patients. Methods: Between January 2013 and December 2014, 4,815 breast cancer patients were available for survival analysis using an established claims-based method. These patients were filtered to include those with clear mapping to treating oncologists and treating institutions. To measure each institution’s level of Integrative involvement, a scoring system was developed with the Samueli Foundation and oncologists from each institution were surveyed on the education, availability, and financing of 12 complementary and lifestyle approaches during the treatment timeframe. Statistical analysis using multivariate modeling with logistic regression and a lasso approach were employed. 19 variables across region, patient demographics, and institutional profile were included. Model coefficients are exponentiated and presented as odds-ratios, with less than one having a negative impact on survival and greater than one improved survival. Results: We identified 173 patients mapping to 103 institutions and 103 oncologists who responded to our survey. Median age of breast cancer patients was 51 (range: 32-76). 14 of the patients (8%) were identified as metastatic. The 5-year overall survival among the Low scoring institutions was 89%, Low-Mid 96%, Mid-High 96%, High 95%. Chi square testing across these cohorts showed no statistically significant difference between them. On multivariate modeling, age, geography, metastatic status, academic setting, and Integrative score were predictors of 5-year survival. The most significant 9 variables are shown in Table. Having metastatic disease, treatment at a non NCCN designated facility, treatment at Midwest or Western Region predicts for lower 5-year survival. Older age, treatment at an academic setting, and having a High or Low-Mid Integrative score are predictors of improved survival. Conclusions: This study suggests that in addition to traditional predictors of survival such as metastatic disease and younger age, patients receiving treatment at an institution that supports Integrative Oncology programs may be associated with improved survival. More work is needed to evaluate the relationship between Integrative Oncology and cancer treatment outcomes.[Table: see text]
Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.
Authors: Alasfour Maryam , Alawadi Salman , AlMojel Malak , Costa Philippos Apolinario , Barreto Coelho Priscila , Plate Thomas , Ahn Soyeon , Lopes Gilberto
Published: June 2021

e18600

Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.
Optimism bias in the design of phase III randomized control trials (RCTs) evaluating PD-1/PD-L1 targeting monoclonal antibodies (mAbs).
Authors: Al-Showbaki Laith , Almugbel Fahad , Alqaisi Husam , Amir Eitan , Chen Eric Xueyu
Published: June 2021

e18616

Background: PD-1/PD-L1 targeting monoclonal antibodies (mAbs) improve outcomes in multiple cancer types. Multiple mAbs are in clinical development, and many randomized control trials (RCTs) have been completed or are in progress. These RCTs compete for limited clinical trials infrastructure, human resources and patients. Since the hypothesized benefit of an intervention is a critical determinant of the number of patients required for an RCT, it is crucial that the expected benefit be estimated appropriately. We examined the hypothesized hazard ratio (HHR) and the observed hazard ratio (OHR) in RCTs evaluating PD-1/PD-L1 targeting mAbs. Methods: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary publication for each RCT and its associated protocol were retrieved. Two investigators independently extracted HHR, OHR for the primary endpoint among other data elements. The differences (∆HR) in HHR and OHR were analyzed statistically. Updated OHRs (uOHR) were extracted from reports with extended follow-ups. Results: 49 RCTs enrolling 36867 patients were included. 45/49 RCTs were in the palliative setting. HHR was met or exceeded in 22 (45%) RCTs. The mean HHR and OHR were 0.672 and 0.738, respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895, 95% confidence interval = 0.003 – 0.130). A lower magnitude of effect than hypothesized in 12/29 RCTs in non-small cell lung cancer, melanoma and renal cell carcinoma, but in 15/20 RCTs in other cancer types. OHR was ≥ 1.0 in 6 RCTs (12%). In the palliative setting, ∆HR was larger in more heavily pre-treated patients. PD-L1 expression was not associated with magnitude of effect. However, a higher magnitude of effect was observed for RCTs published in the New England Journal of Medicine. For 18 RCTs with extended follow-ups, uOHR was higher than OHR in 8. Conclusions: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of effect. Investigators’ optimism regarding these agents should be combined with more realistic expectations. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in various disease settings.
The use of machine learning for predicating complications of free flap head and neck reconstruction.
Authors: Asaad Malke , Lu Sheng-Chieh , Kambhampati Praneeth , Liu Jun , Chang Edward I , Yu Peirong , Hanasono Matthew , Sidey-Gibbons Chris
Published: June 2021

e18633

Background: The use of machine learning (ML) in plastic and reconstructive surgery has increased over the last decade. However, its use to predict surgical outcomes in head and neck reconstruction has not been well studied. The goal of this study is to assess the performance of ML algorithms trained to predict surgical outcomes of head and neck free flap reconstruction. Methods: Our study cohort included routinely collected data from 4000 patients who underwent free flaps for reconstruction of head and neck defects between January 2005 and December 2018. We developed and tested nine supervised ML algorithms to predict three outcomes of a.) any complication, b.) any major recipient-site complication, and c.) total flap loss. Results: In our sample, 33.7% of patients experienced any complication, 26.5% experienced a major complication at the recipient site and 1.7% experienced total flap loss. The k-nearest neighbors algorithm demonstrated the best overall performance for predicting any complication (AUROC = .61, sensitivity = .60). Regularized regression had the best performance for predicting major recipient site complication (AUROC=.68, sensitivity = .66), and decision trees were the best predictors of total flap loss (AUROC = .66, sensitivity = .50). Conclusions: We demonstrated that ML models trained using routinely collected data can make clinical useful predictions about who will experience complications. Our models correctly identified between half and two-thirds of patients who experienced post-surgical complications including total flap loss. These models can be applied to readily available clinical and perioperative data to facilitate decision making. Further performance improvements are likely possible with the inclusion of additional variables related to patient health and behavior.
Animated patient’s guide to lung cancer enables shared decisions and improves health outcomes.
Authors: Patel Manish , Blackmon Shanda H. , Dudek Arkadiusz Z. , Fujioka Naomi , Kern Shirley , Torrison Nancy , Janne Pasi A.
Published: June 2021

e18634

Background: Informed patients have better health outcomes. In a study of 1,057 patient encounters with 3,552 clinical decisions, only 9% resulted in informed medical decisions.The complexity of treatments and patients' limitations in health literacy (especially common in underserved communities) make it difficult for patients to engage in SDM. In 2017, A Breath of Hope Lung Foundation introduced An Animated Patient’s Guide to Lung Cancer (APG), an online resource aimed at improving patient knowledge. Methods: APG consists of animations, expert FAQ videos, slide shows, infographics, patient-experience videos, knowledge-assessment tools, and learner feedback. Video views, duration of use, and learner responses to multiple-choice questions on the APG website were collected for 33 months – through August 2020. Total APG views, most frequently viewed animations and expert videos were monitored on the website and on YouTube, to measure learner responses to outcome-based questions, and learner intent-to-implement changes. Results: 212,336 total views: 142,998 unique visitors: 59% from U.S. and 41% from 50 other countries. Unique U.S. visitors: 43,872 patients, 16,030 caregivers, and 7,593 health providers. 94% reported they will ‘use new information to better self-manage their lung cancer’ (n = 277); 98% ‘will discuss information learned with their doctor’ (n = 455), and 93% ‘plan to discuss treatment options with their doctor’ (n = 272). Conclusions: Multimedia ‘animated’ formats of learning tailored to the needs and learning styles of lung cancer patients provides effective learning, informed patients, increased management skills, and improved engagement in shared decision making.
Practice transformation at scale through a microsystems quality improvement (QI) approach.
Authors: Gordan Lucio N. , Chaudhry Basit Iqbal , Hussein Maen A. , Connor Nora , Yue Andrew , Diaz Michael , Strickland T. R. , Tran Lisa , Walcker Nathan
Published: June 2021

e18667

Background: How oncology providers should implement practice transformation for value-based care is unclear, particularly at scale. Organizational size enables efficient “top down” approaches, but also presents challenges such as physician engagement. Dis-economies of scale can be acute in oncology due to physician autonomy and coordination costs. We hypothesized that organizational change based in sense-making models that enhance physician engagement and use a decentralized, iterative microsystems approach will enable practice transformation to scale. Methods: Florida Cancer Specialists & Research Institute (FCS) is a physician led 250-oncologist statewide practice, with regional variation in disease state/mix, patient cohort, etc., making a purely top-down approach to organizational change infeasible. FCS prototyped a transformation strategy starting in June 2017 based on sharing interpreted data with physician and executive leadership. Later implementation directly engaged physicians in a microsystems quality QI strategy focused on regional performance. Interventions targeted disease, health service utilization, location, and individual physicians. Performance was evaluated using data from Medicare’s Oncology Care Model (OCM) and assessed using the one-sided risk target (4% below benchmark). We analyzed 70,239 performance period (PP) episodes at FCS across 35,116 patients. Results: In the pre- intervention period (90% of PP1 episodes, completed by June 2017), FCS was 5.8% above target. Performance was 10.9% above target for the remainder of PP1 (10% of PP1 episodes), then improved to 0.3% above target in PP2 and PP3, and below target by 0.9%, 0.8%, and 0.75% in PP4, PP5, and PP6. Early QI efforts focused on performance in lung cancer, which was 2.5% over target in PP1; it improved to 2.1% under target in PP6. Later regional QI sessions targeted cancer, utilization and providers. Pre-intervention, all 18 regions were above target; by PP6, 11 out of 19 regions were below target. Relative to the pre-intervention period, per-episode inpatient costs increased by 12.1% for the remainder of PP1 and increased by 4.3% and 1.3% in PP2 and PP6; inpatient costs decreased in PP3, PP4, and PP5 by 3.8%, 2.4% and 4.8%. Conclusions: Practice transformation in oncology can achieve scale through models of organizational change that foster physician engagement. Data, when clinically contextualized, is a foundational tool in the sense-making process. Scale can develop through an additive microsystems approach in which QI units are de-centralized, accountability is defined, and iteration becomes part of organizational culture. [Table: see text]
Descriptive cross-sectional analysis of lung cancer screening in inner city resident run clinic.
Authors: Singh Meghana , Kulkarni Radhika , Lopetegui-Lia Nerea , Vredenburgh James J.
Published: June 2021

e18668

Background: Lung cancer is one of the leading causes of cancer-related morbidity and mortality. The 5-year survival rate is 19% but goes up to 57% if diagnosed at early stage. The recommendation for lung cancer screening is low-dose computed tomography (LDCT) for adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit in the past 15 years. Unfortunately, less than 5% of eligible patients undergo LDCT. Methods: A retrospective chart review was done for patients with any smoking history, who had internal medicine residents as their primary care provider. The data collected included baseline characteristics and the rates of LDCT scan being ordered and completed. Results: 706 medical charts were reviewed. 178 patients (25.2%) qualified for LDCT screening. The average age of patients included was 64.41 years and average BMI was 28.8 kg/m2. 48.3% were female and 51.6% were male. 54% were current smokers and 46% were former smokers. The ethnic/racial distribution was as follows: 19% African American, 36.5% Hispanic,16.2% Caucasian and 27.5% belonging to other groups. The primary insurance was as follows: 48.8% Medicaid, 19.6% Medicare, 25.8% private insurance and 5% were uninsured. 95 patients (53.3%) had a LDCT scan ordered and 73/95 (76.8%) completed the LDCT scan. The rate of compliance among patients based on their race/ethnicity and primary insurance is detailed in the table. Only 30% of the patients initially screened had a follow up LDCT ordered in one year. Conclusions: Low screening rate LDCT may be due to new residents not prioritizing preventative care. Patients at this clinic belong to a lower socioeconomic class with limited resources. There may be barriers to completion of the ordered test, like poor health literacy, scheduling issues, transportation, fear of being diagnosed with cancer and poor understanding of preventative health. Residents need to be educated about the importance of lung cancer screening as early detection translates into better outcomes and lower mortality. Patients need to be informed of the benefit of screening to improve compliance rate. Assessing the barriers these patients face to completing the screening test should also be carefully evaluated to better identify areas of improvement.[Table: see text]
Improving the inclusion rate in clinical trials of bladder cancer despite COVID-19 pandemic by using ASCO quality training program.
Authors: Vidal Natalia , Gomez Juan , Galante Isabel , Senovilla Jose Luis , Gonzalez-Larriba Jose-Luis , Toledano Carmen , de la Parra Irene , Jerez Tamara , Fernandez-Montarroso Lorena , Redondo Enrique , Moreno Jesús , Perez Pedro , Puente Javier
Published: June 2021

e18674

Background: In 2019, we used the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) as an instrument to improve the inclusion rate in clinical trials (CTs) for bladder cancer patients from 24% in 2018 to 43,75% in 2019. CTs play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. Therefore, we believe it is important for patients and for society to maintain the inclusion rate in clinical trials despite COVID-19 pandemic. Methods: We collected the number of bladder cancer patients evaluated for the first time in the Oncology department, the number of patients who were offered a clinical trial, the screen failures and the number of patients enrolled in CTs. Results: In 2019, we were able to increase the enrollment rate in CTs for bladder cancer patients to from 24% to 43,75% thanks to the ASCO-QTP. With this program we created a list of measures and identified the ones that would have a greater impact. The one that seems to have had the highest impact is the diffusion of CTs in the Investigation Unit and the Genitourinary (GU) board. In 2020, thanks to this measure and despite the COVID-19 pandemic, we were able to maintain a 40,81% enrollment rate. When analyzing the patients evaluated for the first time in the Oncology department, 48 in 2019 and 49 in 2020, there were some interesting differences. In 2020, 42,86% had stage IV disease with respect to 39,6% in 2019, and only 22,44% had non-muscle invasive disease (NMIBC) versus 33,33% in 2019. However, thanks to the diffusion of CTs in the Investigation Unit and in the GU-board, which translates in an early derivation of patients to Medical Oncology and an increase in the number of available CTs, we were able to offer a CT to 73,5% of patients in 2020 against 60,4% in 2019. Although there was an increase of screen failures in 2020 (32,65% vs. 16,66%), 50% of them were due to the absence of a biomarker in a biomarker driven CT, with respect to 25% in 2019. Conclusions: Using ASCO-QTP as an instrument, we identified the importance of the diffusion of CTs and the close collaboration between departments. Maintaining these measures, we were able to uphold the inclusion rate in CTs for bladder cancer patients in 40,81% despite the later diagnosis of patients due to COVID-19 pandemic.
Social distancing to avoid SARS-Cov-2 infection in cancer and non-cancer patients.
Authors: Kloecker Goetz H. , Ellis Jason , Korbee Leslie , Nolan Joseph , Calhoun Royce , Logan Barbara , Flora Daniel Blake , Flora Douglas B. , Hartman Philp
Published: June 2021

e18697

Background: Social distancing has been recommended by the CDC to avoid exposure to SARS-CoV-2. Cancer patients on or after active therapy appear to be more prone to COVID being symptomatic and life threatening. When evaluating cancer patients’ risk of acquiring COVID it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared to non-cancer patients and what factors lead to the decision to distance oneself. Methods: After a pilot phase using patients MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap. Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and non-cancer patients. Demographics, comorbidities and a questionnaire about anxiety (GAD-7 scale for Generalized Anxiety Disorder) were recorded. To assess differences between cancer and non-cancer groups Bonferroni-corrected chi-square tests and proportions confidence intervals were used. Results: The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. 387 cancer patients (32.4% responded and 503 non-cancer (22.9% responded) patients completed the survey. Questions about leaving their house, driving, shopping, friends and family indicated that patients with cancer are more cautious (p < 0.001). Cancer patients were up to 20% more likely to distance themselves. No evidence of a difference was seen in wearing a mask, at least 85 % most of the time. A majority of respondents were female (63% vs 71%). Cancer patients were older ( > 60 years, 69 % vs 45%) and less likely to work (52% vs 31%) or less likely to be white collar workers (21% vs 38%). There was no difference of the anxiety score in both groups (not at all anxious, 54%). Conclusions: Cancer patients’ responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear, which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID’s impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.
Treatment patterns, overall survival, and healthcare utilization among Medicare beneficiaries with endometrial cancer in the United States.
Authors: Gokhale Mugdha , Ma Jiemin , Shao Changxia , Chen Lei , Orlowski Robert
Published: June 2021

e18698

Background: Endometrial cancer (EC) is the most common gynecologic cancer in the US, yet real-world disease burden is poorly understood. To address this, we conducted a retrospective study exploring patient (pt) characteristics, treatment patterns, overall survival (OS), and healthcare resource utilization (HCRU) among elderly US pts with EC. Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data, we identified beneficiaries aged ≥65 y with newly diagnosed EC between Jan 1, 2007–Dec 31, 2013. Pts were followed from the EC diagnosis date to the earliest of death, loss to follow-up, or Dec 31, 2014. Descriptive analyses were conducted for pt characteristics assessed in the 6-mo baseline period and for treatment patterns and HCRU assessed during follow-up. Median OS was estimated from the start of each line of systemic therapy using the Kaplan-Meier method. Lines of therapy started when pts received a new systemic therapy regimen and ended when pts switched to another regimen, after a 90-d treatment gap, or at end of follow-up. For pts with surgery, systemic therapy starting >120 d after surgery or after discontinuation of adjuvant therapy was defined as first-line (1L) therapy. Adjuvant therapy was defined as any systemic therapy starting ≤120 d after surgery for EC and ending after a 90-d treatment gap following the last prescription. Results: There were 12,710 eligible pts with EC during 2007–2013 in the SEER-Medicare database; median age at diagnosis was 73 y. At initial diagnosis, 9395 (73.9%) pts had stage I/II EC, 2042 (16.1%) had stage III, and 1273 (10.0%) had stage IV. 778 pts did not receive surgery/radiation, 1230 pts received surgery/radiation plus adjuvant therapy, 9729 pts received surgery/radiation only, and 973 (7.7%) pts received 1L systemic therapy. Of these 973 pts, 370 (38.0%) received second-line (2L) and 157 (16.1%) received third-line (3L) treatment. Pts receiving 1L therapy had a mean of 5.6 outpatient physician office visits per month, 22.1% had ≥1 hospitalization, and 38.5% had ≥1 emergency room visit during follow-up. Carboplatin-based regimens were the most frequently used 1L therapies (56.8%), typically combined with paclitaxel (43.5%). Median OS was generally short, particularly for those diagnosed with stage III/IV EC (Table). Conclusions: Medicare beneficiaries receiving systemic chemotherapy for EC generally had high HCRU and poor survival, particularly among pts diagnosed at later stages. This highlights the underlying disease burden and unmet need for more effective treatments in these pts.[Table: see text]
The present scenario of colorectal cancer in Southeastern Brazil.
Authors: Pulido Jose Zago , Aleixo Sabina B. , Parmanhane Narelle , Sogame Luciana
Published: June 2021

e18782

Background: Cancer is the second leading cause of death in the world and in Brazil. Most of colorectal cancers (CRC) are sporadic and occur in individuals over the age of 50. Since almost all CRC originate from a polyp , the early detection and excision of an adenomatous polyp is essential to avoid the adenoma-carcinoma sequence that occurs over the years. Most colorectal polyps are asymptomatic and identified during screening colonoscopies or in patients with positive fecal occult blood test . There is evidence that detecting and removing these cancer precursor lesions can prevent many cases of cancer and reduce mortality. The CRC are public health problem in Brazil and fulfills criteria to merit the implementation of a structured screening program. and in this sense, several medical societies recommend screening through organized programs and not just opportunistic as done in Brazil. It is believed that this strategy is related to late diagnosis and has impact on high mortality. Most evidence on CRC screening interventions comes from high-income countries. The large disparities in CRC incidence and mortality rates between high-income and low-income countries are attribute to screening. The study will evaluate the stage of colorectal cancer at diagnosis at Southeastern Brazil. Methods: We collected retrospective data of patients with CRC registered in the Hospital Evangélico de Cachoeiro de Itapemirim (HECI) Health Information System - SISRHC from 2010 to 2017 to know the clinical characteristics (TNM) of the patients diagnosed during this period, age and sex. From January 1, 2010 to December 31, 2017, 6,962 newly diagnosed cases of cancer were identified. Of this total, 676 (9.7%) were new cases of colorectal cancer. When submitting to the inclusion and exclusion criteria of the present study 91 cases were excluded (1 case under the age of 18 years; 64 cases that started their first cancer treatment before the pathological result; 26 cases without information from the anatomopathological diagnosis). Data from the remaining 585 cases were analyzed. Results: Among 585 analyzed, the distribution of stage at diagnosis was : 0 (0,68%), I 45 (7,69%), II 109 (18,63%), III 225 (38,45%), IV 129 (22,05%) and 73 (12,48%) had this information missing. Mean age at diagnosis was 62 years, with 411(70,50%) between ages 51-80 years. Regarding sex we found 306 (52,49%) male and 277 (47,51%) female. Conclusions: The results found in the studied population are in agreement with the literature regarding age at diagnosis and sex. Unfortunately demonstrates that most of colorectal,cancer in southeastern region of Brazil are diagnosed in late stages. The lack of screening is an explanation to this fact. Only the implemention of national organized screening program can improve cancer detection and provide better chances of cancer survival.
FDA Oncology Center of Excellence landscape analysis of real-world data submissions for oncology drugs.
Authors: Rivera Donna , Lee Jennifer J. , Royce Melanie E , Kluetz Paul Gustav
Published: June 2021

e18787

Background: Aligning with 21st Century Cures legislation, the FDA is exploring trial design modernization and methodology to advance appropriate uses of Real World Data (RWD) to generate Real World Evidence (RWE). The Oncology Center of Excellence RWE Program was established in 2020 to advance RWE efforts specific to oncology drug development. Inclusion of RWD to support regulatory decision making has increased in oncology, and a landscape analysis was conducted to characterize the RWD included in submissions. Methods: A systematic search was conducted using internal FDA databases to identify RWD submissions from 2010 to 2020. Search terms included: real world evidence, real world data, electronic health record, cancer registry, administrative claims, external control arm, observational cohort, historical control arm, rwOS, rwRR, rwCR, and rwORR. Relevant regulatory submissions were reviewed, and pre-defined common data elements were extracted. A team of FDA reviewers assessed agreement through subset validation (20%). Descriptive statistics were calculated. Results: A total of 142 regulatory submissions included RWD from 2011 to 2020. A subset of 94 submissions met the criteria for evaluation, consisting of 78 unique studies evaluating 56 molecular entities. RWD submissions increased substantially over time, with 28 submissions in 2020. Nearly half of the RWD submissions were for solid tumor indications (68%), with lung cancer being the most predominant site. More than one third of the RWD submissions (37%) were for rare indications. The most common primary RWD study objective was effectiveness (62%) and the most commonly referenced RWD source was EHR/clinical data (54%). The most frequently used primary RWD endpoints were survival (rwOS, 35%) and response (rwORR/PR/BTR, 31%) outcomes (Table). Conclusions: Our review demonstrates a dramatic increase in RWD submissions to support FDA oncology drug development programs. Submissions included a variety of study objectives, data sources, and endpoints. While this landscape analysis provides a picture of potential regulatory objectives, the adequacy of each proposal to support regulatory decision making was not evaluated. Establishing a set of clear regulatory objectives can help advance the development of metrics for robust data characterization and outcome validation to ensure that RWD can be appropriately evaluated and provide the rigor necessary to be considered adequate RWE.[Table: see text]
Effect of healthcare fragmentation on breast, stomach, and colorectal cancer mortality in Colombia: A measurement estimated through administrative databases.
Authors: Rozo Agudelo Nicolás , Saldaña Espinel Laura Estefania , Patiño Benavidez Andres Felipe , Gamboa Garay Oscar Andres , Buitrago Giancarlo
Published: June 2021

e18808

Background: Fragmentation in healthcare leads to adverse outcomes in cancer patients. Currently there is no fragmentation measurement that has been acknowledged to reliably assess healthcare fragmentation across different health systems. We aimed to measure cancer healthcare fragmentation through administrative databases in Colombia and to calculate its effect on breast, stomach and colorectal cancer mortality. Methods: We conducted a cohort study based on health administrative databases from 2013 to 2017. We combined data from two Colombian national health databases (Capitation Payment Unit database and Vital Statistics from DANE). We developed an algorithm based on ICD-10 codes and oncological procedures to select incident cases of breast, stomach and colorectal cancer. To measure healthcare fragmentation, we identified the number of providers between the dates of the first and last registered services. For patients who died during observation we adjusted the number of providers for survival time in days, otherwise survival time was set to 31 december, 2017. We categorized fragmentation in quartiles and evaluated its effect on mortality rate by Kaplan Meier estimates. Results: We identified three cohorts of patients based on primary tumor site. Age distribution was similar in stomach and colorectal cancer. Fragmentation measured as a continuous variable has a non-parametric distribution in all cohorts. The median of follow-up time ranged between 2.4 to 4.4 years. All-cause mortality rates were highest in stomach cancer, lowest in breast cancer. When measured as quartiles, fragmentation has a consistent dose-response effect increasing all-cause mortality rates. Conclusions: Healthcare fragmentation can be measured through algorithms applied to administrative databases in Colombia. Fragmentation is a predictor for all-cause mortality across different oncologic populations. This measurement based on real-world national administrative data could be used as an indicator of high-quality oncological healthcare for the Colombian healthcare system.[Table: see text]
Modeling Medicare’s Oncology Care Model bundles at more clinically granular levels: Evaluating the impact on provider performance.
Authors: Yue Andrew , Connor Nora , Gordan Lucio N. , Tran Lisa , Chaudhry Basit Iqbal
Published: June 2021

e18854

Background: Aggregating different subtypes of cancers into bundles is an important methodology in oncology payment reform as an alternative to fee for service. However, expected resource utilization can vary significantly across cancer subtypes. We evaluated the impact that modeling Chronic Leukemia into a more clinically granular two part framework of chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia would have on OCM results and the risk that the distribution of clinical subtypes at a practice would influence overall performance in the bundle. Methods: OCM episodes of chronic leukemia initiating between July 2016 and June 2019 were subdivided on the basis of individual ICD-10 coded diagnoses on cancer-related E&M visits. From a total of 4,658 episodes, we randomly sampled with replacement 3,500 episodes from 16 practices using empirical data distributions. Data models and mappings were developed based on clinical knowledge and exploratory data analyses to subdivide the OCM bundle of Chronic Leukemias into CLL and CML. Total cost of care and episode target prices were calculated through implementation of the OCM methodology. The distributional consistencies of episode target, cost, cost above target, and percent above target for the two diseases were evaluated by two-sample Kolmogorov-Smirnov (KS) tests. Results: The CML and CLL subtypes modeled from the aggregate OCM bundle demonstrated significantly different cost distributions relative to each other. As anticipated, treatments used in each subtype varied significantly marking different patterns of expected resource utilization. In our model, CLL episodes were on average 13.7% over target. Average CLL episode costs were $52.2K vs. an average target of $47.6K with 54% of episodes running over target. In contrast, CML episodes were 6.1% under target. Average CML episode costs were $45.2K vs. an average target of $50.3K with 43% of episodes running over target. Conclusions: Value based payment models in oncology such as OCM can be improved by modeling cancer bundles in more clinically granular ways that better reflect expected resource utilization for appropriate, standard of care. Insufficient clinical granularity in bundle construction can lead to provider performance being influenced by the distribution of patient subtypes at the practice. This can lead to inappropriate shifts of risk from payers to providers in value based models. Aggregate vs. subtype episode costs (mean, 5th, and 95th percentiles).[Table: see text]
Effect of induction intensity on survival in patients with acute myeloid leukemia.
Authors: Sahasrabudhe Kieran , Rebechi Melanie , Huang Ying , Behbehani Gregory , Bhatnagar Bhavana , Blachly James Stewart , Blaser Bradley Wayne , Borate Uma , Garzon Ramiro , Haque Tamanna Zohra , Larkin Karilyn T.M. , Long Meixiao , Mims Alice S. , Saad Ayman A. , Vasu Sumithira , Walker Alison R. , Wall Sarah Allison
Published: June 2021

e19004

Background: Acute Myeloid Leukemia (AML) has traditionally been treated frontline with intensive induction chemotherapy in patients fit enough for this treatment. The FDA has approved several oral targeted therapies for AML in recent years. The survival impact of these agents vs induction chemotherapy is unknown. Methods: In this single-center, retrospective study, patients diagnosed with AML from 2015-2020 were included if they received treatment with either high intensity chemotherapy (HiC) or lower intensity targeted therapy (LITT). HiC was defined as a regimen containing cytarabine + anthracycline given on a “7+3” based schedule. Patients treated with liposomal cytarabine-daunorubicin were excluded. LITT was defined as venetoclax, gilteritinib, enasidenib, or ivosidenib alone or in combination with a hypomethylating agent. Patients fell into four groups: HiC only, LITT only, HiC followed by LITT, and LITT followed by HiC with assignment censored at transplant. Overall survival (OS) was estimated using Kaplan-Meier method and patients receiving any HiC vs LITT only were compared using log-rank test. Results: A total of 332 patients were included: 177 received HiC only, 116 LITT only, 32 HiC before LITT, and 7 LITT before HiC. Baseline characteristics and OS data are outlined in the table. The any HiC group had a lower median age and more patients with WBC >10 K/µL at diagnosis, as well as more patients receiving allogeneic hematopoietic cell transplant (HCT). OS was superior in the any HiC group vs LITT only group. Receipt of any HiC remained predictive of OS after adjusting for age (HR 0.65, 95% CI 0.44-0.96, p = 0.03); however, was no longer predictive of OS after adjusting for age and receipt of HCT. Conclusions: While HiC was associated with superior OS compared to LITT only treatment in univariable analysis, the survival benefit was no longer apparent after adjusting for age and receipt of HCT. The results suggest that intensity of AML treatment is less impactful on prognosis than ability to receive HCT. Differences in age were likely confounded by clinical trial eligibility and prescribing information specifically affecting patients receiving LITT. In the era of LITT, prospective randomized studies of intensity of AML therapy, particularly in non-favorable risk disease, are imperative to striking a balance between toxicity and cure for patients of all ages.[Table: see text]
Comparative study on iron content detection by energy spectral CT and MRI in MDS patients.
Authors: Zhang Yao , Xiao Chao , Li Jing , Song Lu-Xi , Zhao You-Shan , Han Shuang , Li Zhao-Wei , Guo Cha , Zhao Jun-Gong , Chang Chun-Kang
Published: June 2021

e19032

Background: Myelodysplastic syndrome(MDS) patients may have iron overload due to long-term RBC transfusion or combined with abnormal iron metabolism.what are the differences of iron content detection by magnetic resonance imaging (MRI) and dual energy spectrum computed tomography (DECT)? What are the advantages and disadvantages of the two methods in the state of high and low iron deposition? Can the two methods complement each other? The purpose of this study was to compare the difference of liver/cardiac iron content detection in MDS patients by DECT and MRI under different adjust serum ferritin (ASF) levels. Methods: Liver and cardiac iron content were detected by DECT and MRI. Patients divided into different subgroups according to ASF. Compared the detection rate between DECT and MRI group, and correlation between liver/cardiac iron content detected by DECT/MRI and ASF in each subgroups. Results: The detection rate of iron overload(IO) in DECT group was lower than that of MRI group with ASF < 1000ng/ml subgroup,DECT and MRI had similar detection rates of moderate to severe IO with 1000≤ ASF < 5000ng/ml subgroup, detection rate of severe IO in MRI was lower than that of DECT with 5000ng/ml ≤ ASF subgroup. In patients underwent DECT and MRI examination at the same time, ASF was significantly correlated with hepatic VIC but not with liver iron concentration (LIC), and LIC correlated with ASF after removed these data of ASF > 5000 mg/L. LIC expression are not significantly different among 1000≤ ASF < 5000ng/ml and 5000 ng/ml ≤ASF subgroup. LIC and liver virtual iron content (VIC) were all significant correlation with ASF when ASF < 2500ng/ml, liver VIC was still correlation with ASF but LIC was not when 2500ng/ml≤ ASF. Neither cardiac VIC nor myocardial iron content (MIC) correlation with ASF in these subgroups. Conclusions: This study showed that MRI and DECT can be used complementary to each other. In high iron content, such as ASF ≥5000ng/ml, DECT detection is more reliable. In patients with low iron content, such as SF < 1000 ng/ml, MRI detection is more reliable. According to ASF, the appropriate detection method can be selected to evaluate the iron content more accurately.
Outcomes with venetoclax in myelodysplastic syndromes: A systematic review.
Authors: Khanam Razwana , Shahzad Moazzam , Pachika Pranali Santhoshini , Ahmed Zahoor , Ali Fatima , Masood Adeel , Shah Zunairah , Chattaraj Asmi , Chaudhary Sibgha Gull , Balusu Ramesh , Ahmed Nausheen , Khurana Sharad , Anwer Faiz , Abhyankar Sunil H. , McGuirk Joseph P , Mushtaq Muhammad Umair
Published: June 2021

e19035

Background: Myelodysplastic syndromes (MDS) are clonal hemopoietic disorders causing cytopenia(s) and increased risk of transformation to acute myeloid leukemia (AML). Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor that induces apoptosis in malignant cells. The FDA has approved venetoclax for the treatment of newly diagnosed adult AML patients unfit for intensive chemotherapy and its utility in MDS is being explored. We present a systematic review aimed to evaluate outcomes with venetoclax in MDS patients. Methods: We performed a literature search on 3 databases (Pubmed, Cochrane, and Clinicaltrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We screened 62 studies using the Mesh terms ‘myelodysplastic syndrome’ and ‘venetoclax’. After excluding review, duplicate and non-relevant articles, 8 studies were included in the analysis. Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the ‘meta’ package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. The Inter-study heterogeneity among the studies was assessed using the Q statistic proposed by Cochrane and the I2 index introduced by Higgins and Thompson. Results: We identified 313 patients from 8 studies (1 prospective, 3 retrospective, 2 ex-vivo, 2 clinical trials). Venetoclax was used in combination with hypomethylating agents (HMA) in 6 studies and with other agents in 2 studies. Most patients were pre-treated. Complete response (CR) with or without hematological recovery (CRi) was reported in 45% of patients (95% CI 0.26-0.66, I2= 90%, n = 292). Stable disease (SD) was seen in 18% patients (95% CI 0.08-0.37, I2= 85%, n = 223). Overall response rate (ORR) was 51% (95% CI 0.31-0.70, I2= 89%, n = 122). Hematopoietic stem cell transplant (HCT) was performed in 22% patients (95% CI 0.09-0.44, I2= 75%, n = 122). Twenty percent patients (95% CI 0.15-0.28, I2= 0%, n = 149) died. Common adverse events seen with venetoclax were cytopenias, gastrointestinal side effects and infections, often requiring drug interruption or dose. Conclusions: Despite heterogeneity of available literature, venetoclax seems to be a promising agent in treatment of MDS patients. Prospective clinical trial data is needed to ascertain safety and efficacy of venetoclax in MDS and impact on overall survival, in particular, in patients proceeding to HCT.[Table: see text]