bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and severity of neutropenia in patients treated with cyclin-dependent kinase 4/6 inhibitors (CDKi) for metastatic breast cancer.
Authors: Singh Anmol , Giordano Sharon H. , Zhang Ning , Chavez Mac Gregor Mariana , Zhao Hui
Published: June 2022

e13036

Background: Palbociclib (P), ribociclib (R), and abemaciclib (A) are FDA approved CDKi used in combination with endocrine therapy for first- and second-line treatment of metastatic breast cancer. Neutropenia is a commonly encountered adverse effect with these agents. This analysis aimed to identify the incidence and severity of neutropenia in patients receiving CDKis. Methods: This retrospective, observational study used administrative data from the Optum’s de-identified Clinformatics® Data Mart Database (January 2016-June 2020) to identify patients treated with P, R, or A and who had at least two ICD-9 or ICD-10 diagnosis codes for breast cancer separated by >30 days. Using claims, neutropenia was defined as either one inpatient diagnosis code or 2 outpatient diagnosis codes from the time of the patient’s first CDKi prescription claim to the time of the last claim plus 42 days. For the subset of patients who had laboratory results during their period of treatment with CDKi, neutropenia was defined as an absolute neutrophil count (ANC) <1500 and severe neutropenia as ANC <500. Descriptive statistics and logistic regression models were used to characterize the population and to identify risk factors for development of neutropenia. Results: Of the total of 8,158 included patients, 82% were treated with P, 4.1% with R, 7.5% with A, and 6.4% with more than one CDKi. Patient age ranged from 28 to 91 years (median= 68 years). Median follow up from initiation of CDKi until the end was 194 days. 17.5% patients had ICD claims indicating neutropenia but only 1.6% were hospitalized with a diagnosis of neutropenia. Neutropenia codes were observed in 31.6% patients treated with P, 24.6% patients treated with R, and 15.6% patients treated with A. Among the 4766 patients who had laboratory results, 81% were treated with P, 4% with R, 7% with A, and 8% with more than one CDKi. 31.6% of patients had neutropenia defined by ANC < 1500. Severe neutropenia was seen in 10.8% of patients treated with P, 5.7% of those treated with R, and 5% of those treated with A. In a logistic regression model among the patients with lab results, patients treated with P had increased odds of neutropenia compared to those treated with A (OR 1.84, 95% CI 1.40-2.43) but patients treated with R vs A did not (OR 1.46, 95% CI 0.95-2.25). Asian and Hispanic patients had higher odds of neutropenia (OR 1.7, 95% CI 1.2-2.4, OR 2.1, 95% CI 1.8-2.6, respectively) compared to Whites, but Black patients had lower risk than White patients (OR 0.8, 95% CI 0.6-0.9). Conclusions: Neutropenia remains a common side effect of CDKis, although the frequency of severe neutropenia is low. Of the three CDKis, P was associated with the highest rate of neutropenia.
Treatment of alpelisib induced hyperglycemia with sodium-glucose cotransporter-2 inhibitors: A single institution experience.
Authors: Brugioni Emily , Pluard Timothy J. , Cathcart-Rake Elizabeth Jane , Gosch Kensey
Published: June 2022

e13041

Background: PIK3CA mutations occur in about 40% of patients with HR+/HER2- breast cancer. The phase III SOLAR-1 trial demonstrated prolonged progression-free survival with alpelisib and fulvestrant compared to fulvestrant alone among patients with HR+/HER2-/ PIK3CA mutant advanced breast cancer previously treated with endocrine therapy. Hyperglycemia was seen in 64% of patients treated with alpelisib and fulvestrant and was treated with metformin. Inhibition of PI3Kα leads to an on-target effect of hyperglycemia and a secondary hyperinsulinemia. This rebound hyperinsulinemia may lead to escape PI3K pathway activation in breast cancer progression via the insulin and IGF1pathways. Concurrent administration of SGLT2 inhibitors may abrogate the PI3K pathway activation effect and delay disease progression. This study reports time on treatment with alpelisib and PFS among patients who received an SGLT2 inhibitor with alpelisib. Methods: A retrospective review of all metastatic breast cancer patients treated with alpelisib was completed from 8/2019 to 5/2021 at the Saint Luke’s Koontz Center for Advanced Breast Cancer. Results: This review included 22 female patients, 11 received an SGLT2 inhibitor for treatment related hyperglycemia (A+SGLT group) and 11 who received metformin/other diabetic agents (A group). Baseline characteristics were not significantly different between the two groups: median age 63, BMI of 29.1, hemoglobin A1C of 6.3 and fasting blood glucose of 119.1mg/dl. PIK3CA mutations included H1047X (40.9%), E545X (31.8%), E542K (13.6%), other (13.6%). The median number of prior treatments for MBC was 3 (range 1-5). Prior treatments included aromatase inhibitors: 100%, fulvestrant: 77%, CDK 4/6 inhibitors: 82%, everolimus: 32% and chemotherapy: 68%. Hyperglycemia grade 2+ was seen in 72.7% of patients. There were no significant differences between the two groups for emergency room visits, hospitalizations, or endocrinology referrals related to hyperglycemia. Median time to initiation of an SGLT2 inhibitor was 13 days following the first dose of alpelisib. PFS was longer in the A+SGLT compared with the A group with a median time to progression of 6.1 months and 3.9 months respectively (HR 0.51; 95% CI 0.16 to 1.63; p = 0.39). Time on treatment was significantly longer for A+SGLT group compared with the A group, with a median time on treatment of 5.8 months, compared with 3.0 months (HR 0.32; 95% CI 0.11 to 0.92; p = 0.03). The primary reason for discontinuation of alpelisb was disease progression in 73%, with no statistically significant difference in the reason for discontinuation between the groups. Conclusions: This study supports a potential clinical benefit of an SGLT inhibitor along with alpelisib in allowing for a longer time on treatment, without significant adverse events. It also suggests a possible favorable impact on PFS for the combination.
Atrial fibrillation is associated with worse outcomes in patients with breast cancer.
Authors: Gad Mohamed M. , Saad Anas M.
Published: June 2022

e13043

Background: The incidence of atrial fibrillation (AF) is higher in women with breast cancer (BC) compared to aged-matched controls. A better understanding of the clinical outcomes in women with BC and AF can help stratify patients’ risk and inform clinical decision making. Methods: Females with active BC diagnosis hospitalized from January 2010 to December 2018 for any cause were identified in the Nationwide Readmissions Database (NRD). Hospitalizations were divided to females with AF and those without a known diagnosis of AF. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was performed to adjust for differences in baseline characteristics. All statistical analyses were conducted using the weighted values of observations as provided by the NRD to measure national estimates. Results: A total of 1,596,853 hospitalizations of BC were identified. Out of those, 119,307 (7.5%) had AF. Females with AF were older, median age 77 [IQR 69-84] versus 61 [51-71]. AF patients had higher rates of chronic pulmonary disease, 23.0% versus 14.3%, p < 0.001; hypothyroidism, 20.9% versus 13.1%, p < 0.001; peripheral vascular disease, 6.8% versus 2.5%, p < 0.001; pulmonary hypertension, 4.8% versus 1.6%, p < 0.001; cardiac valvular disease, 9.5% versus 2.3%, p < 0.001; hyperlipidemia, 39.9% versus 24.0%, p < 0.001; diabetes mellitus, 28.9% versus 19.8%, p < 0.001; heart failure, 37.0% versus 7.5%, p < 0.001; prior bypass surgery, 4.1% versus 1.2%, p < 0.001; prior stroke, 7.8% versus 2.5%, p < 0.001; and prior myocardial infarction, 6.0% versus 2.2%, p < 0.001. In-hospital mortality was significantly higher in patients with AF, 7.1% versus 4.1%, p < 0.001. Adjusted Odds Ratio (aOR) for in-hospital mortality was higher in AF, aOR 1.42, 95% CI (1.38-1.46), p < 0.001. Conclusions: Atrial fibrillation is associated with a higher risk of in-hospital mortality in patients with breast cancer regardless of the reason of hospitalization. Stratifying patients based on AF presence can help inform clinicians and patients of the patients’ risk of mortality during hospitalization.
PD-L1 immune cell expression levels and clinical outcomes in advanced triple-negative breast cancer treated with atezolizumab.
Authors: Ovcaricek Tanja , Dobovisek Luka , Gasljevic Gorana , Stefanovski Dimitar , Borstnar Simona
Published: June 2022

e13066

Background: Treatment with immune checkpoint inhibitors (ICI) has become a standard of care for metastatic PD-L1 positive TNBC patients and PD-L1 has emerged as an important predictive biomarker. Predictive differences of PD-L1 were found in response to immunotherapy in different studies. Alterations in DNA repair pathways (aDDR) have also been investigated as a predictive biomarker for ICI due to the increased mutations and neoantigen production. Real-world data regarding outcomes of treatment of metastatic (m)TNBC patients (pts) with ICI and predictive value of PD-L1 and aDDR is lacking. In this study PD-L1 and aDDR were evaluated for association with clinical benefit of treatment with atezolizumab and nab-paclitaxel (A+nP) in PD-L1 positive mTNBC patients treated in routine clinical practice. Methods: Medical records from 41 PD-L1 positive mTNBC patients consecutively treated with A+nP at Oncology Institute Ljubljana between April 2019 and October 2021 were collected for the present study. PD-L1 expression was assessed on immune cells (IC) as percentage of tumor area using VENTANA SP142 PD-L1 IHC assay (<1% [PD-L1 negative] vs. ≥1% [PD-L1 positive). Patients were divided into 2 subgroups based on PD-L1 status, high (PD-L1≥ 5%) and low (PD-L1 ≥1% and <5%). Germline alteration status in DDR genes was determined on blood samples. We used Kaplan-Meier survival curves to calculate median (m) PFS and OS . The prognostic impact of PD-L1exspresion levels and aDDR was calculated using Cox model. Results: Median follow up of the study was 22 months. Majority of patients had low PD-L1 status (25/41, 61%) and 54% of evaluable patients (15/28) were found to harbor deleterious alterations in DDR genes, of them BRCA1 in 9 pts, BRCA2 in 2 pts, and PALB2, CHEK2, CHD1, RAD51D in 1 pts. Median PFS in the entire cohort was 8.26 months; 95% CI (3.54-12.98) and mOS 20.49 months; 95% CI (11.3-29.7). Significant survival benefit was observed among patients with high PD-L1 status treated with A+nP. No difference in survival was found in patients harbouring germline mutations (aDDR positive) versus without mutations (Table). Conclusions: PD-L1 positive mTNBC patients with high PD-L1 status (≥5%) had almost three times less risk of progression and death compared to low PD-L1 status (≥1% and <5%). Presence of aDDR showed no effect on disease outcome. [Table: see text]
Preanalytical protocols for improving access to live tissue diagnostics in remote and low resource settings.
Authors: Charania Areesha A. , Patel Heli K. , Punjani Zeenia , Patel Zeelu H. , Papachristou Georgios , Contreras Carlo M. , Tsung Allan , Budhwani Karim I.
Published: June 2022

e13501

Background: Nearly 70% of diagnostics lab test errors occur due to variability in preanalytical factors. Preanalytical factors comprise parameters from the time tissue is extracted from the patient to the time it is tested in the lab. For lack of standardized preanalytical protocols, integrity of collected specimens is often compromised. This is particularly pronounced when specimens are collected in remote or low resource settings and shipped to testing facilities. Establishing preanalytical protocols could serve as an important resource for remote collection sites and substantially reduce variability in the integrity of specimens thereby improving lab test rigor and reproducibility and promote innovation in live tissue diagnostic tests for personalized medicine. Objective: The aim of this study is to analyze impact of cold chain logistics on integrity of collected solid tumor tissue specimens. Specifically, duration in transit, container and wet ice packing, and composition of transport media were assessed. Methods: Baseline protocols for biospecimen preanalytical parameters were established from literature review. Standard aseptic lab protocols were implemented for all experiments including preparation of transport media, tissue transport kits, transport kit packaging, tumor tissue transfer in tissue transport kits, tissue receiving, and tissue integrity assessment. Transport was simulated for human and murine pancreatic ductal adenocarcinoma (PDAC) tissue by holding packaged tumor tissue containers in storage for the duration of transport. Saline solution, basal media, and complete media were evaluated as transport media. Specimen integrity was evaluated using live/dead assays in high-content imaging systems at 24- and 48-hour intervals. Results: For human and murine tumor tissue, viability was optimal when tissue was transported in Nalgene jars containing complete media packaged in ¼” thick wall Styrofoam containers tightly packed in wet ice for transport. While specimens fared well over both 24- and 48- hour simulated shipping durations, temperature and humidity logs from sensors embedded in the packages showed sharp degradation in packaging environment with longer durations of time. Conclusions: Establishing preanalytical protocols would improve rigor and reproducibility in diagnostic lab tests by improving tissue viability and integrity. Such protocols would also enable next generation cancer models to further enhance predictive capacity in translational research and subsequently in personalized medicine applications at the bedside.
Availability of child care resources for patients undergoing cancer treatment at NCI-designated cancer centers.
Authors: Levine Monica , Brown Melissa , Nagel Christa , Vargas Roberto , Chambers Laura
Published: June 2022

e13508

Background: The National Cancer Institute (NCI) estimates that approximately one-quarter of adults with cancer are parents to children less than 18 years. Further, it is estimated that 2.85 million minor children in the United States have a parent undergoing cancer treatment. Previous studies have demonstrated that parents with cancer experience significant stress and disruptions to familial life following a cancer diagnosis. In a study of women with breast, gynecologic cancer and other cancers undergoing cancer therapy, 48.7% of women endorsed needing help with childcare and 64.1% needing help with household management. Despite this evidence supporting both a need for childcare among patients with cancer, data regarding the availability of on-site childcare programs and resources at NCI-designated cancer centers is limited. The objective of this cross-sectional study was to assess the availability of childcare resources for parents who are undergoing cancer treatment at NCI-Designated Cancer Centers. Methods: The availability of childcare resources for parents undergoing cancer treatment at all 51 NCI-designated comprehensive cancer centers and 13 NCI-designated cancer was assessed in January 2021 and February 2021. Childcare resources were assessed via online search and telephone calls. Specifically, centers were queried regarding availability of daycare programs for children of patients undergoing treatment and whether resources were available to assist patients in need of childcare. Descriptive statistics were performed. Results: In total, only 1/64 (1.6%) of NCI-designated cancer centers currently offer childcare resources for patients undergoing cancer treatment. This center offers childcare for children ages 2–8, free of charge with multiple outpatient locations. One additional institution previously provided patients with access to daycare, but has closed due to the COVID-19 pandemic. Further, only 1/64 (1.6%) NCI-designated cancer center offers financial assistance grants to aid patients to subsidizing childcare costs during cancer treatment. Conclusions: Institution sponsored options for childcare for patients undergoing cancer treatments are highly limited, even in the best resourced cancer care settings. The COVID-19 pandemic has limited options further, and many hospitals now restrict visitors under the age of 18. Patient grants or institutionally sponsored childcare provider networks may represent an avenue for supporting parents who are facing a cancer diagnosis. Supporting families of patients with cancer has great potential to impact quality of life, economic and psychological stress.
Impact of turnaround time (TAT) of molecular testing on initial treatment (Tx) in newly diagnosed stage 4 non-small cell lung cancer (NSCLC 4): An Integra Connect (IC) retrospective observational study.
Authors: Gart Mike , Gordan Lucio N. , Choksi Rushir J. , Petro Daniel P. , Scott Jeffrey A. , Varughese Prateesh , Alwon Erin , Smith Robert E.
Published: June 2022

e13510

Background: Broad molecular profile-based initiation of Tx in newly diagnosed NSCLC 4 (KF Mileham, Cancer Med, 2022) is advocated by NCCN guidelines. Despite this, Tx is often started prior to, and without knowledge of, an actionable oncogenic driver (AOD), and often without subsequent switch to appropriate tyrosine kinase inhibitor (TKI). In this study we sought to assess the impact of TAT of genomic testing on Tx in patients harboring a potentially actionable EGFR mutation. Methods: By interrogating the IC curated database, we identified 2,357 newly diagnosed NSCLC 4 patients (pts) who started an initial line of therapy (LOT 1) between 1/1/2019 and 12/31/2021. Squamous carcinoma pts were excluded unless documented to be never smokers or <age 40. We assessed testing across all sample types and performed the analysis on solid tumor tissue next-generation sequence (NGS) tested patients. We used an order for EGFR as a surrogate for AOD evaluation and collected date of order and reporting of EGFR test results, and date of 1st Tx start. From this, we calculated TAT and whether Tx was initiated after genomic results. In addition, we captured whether testing was in-house or by reference lab (RL). We looked at the RLs that comprise of the top 85% of NGS test sources, where the testing source was known. We removed records where test order dates and results dates were the same date, where test order dates or results dates were unknown, and where TAT > 90 days. EGFR Effective Testing Rate (EETR) is defined as EGFR result prior to line 1 Tx start. Results: Median age was 70 (range 40 - 89) and 50% male. Pts with TAT of ≤7 days had an 82% EETR vs. Pts with TAT of >29 days had a 61% EETR. Overall, RLs had a median TAT of 19 days with a 72% EETR, whereas in-house labs had a median TAT of 15 days with a EETR of 80%. Conclusions: When providers and patients can obtain test results within 21 days of test order there is a higher likelihood of waiting for the test result to start Tx. Many community oncology practices are contemplating implementing in-house testing solutions to improve rates of testing and turnaround time of testing. This may prove to be an effective strategy given the better TAT for in-house testing. When there is faster TAT, patients and providers wait to start initial Tx. Getting patients on appropriate therapy based on their biomarker status can improve overall survival.[Table: see text]
Increasing advance directive completion within the 4R oncology model in breast cancer patients prior to surgery in a racially diverse patient population.
Authors: Ossowski Stephanie , Lyon Liisa , Linehan Elizabeth Shurell , Gordon Nancy P. , Egorova Olga , Mark Becky , Beringer Kimberly , Abbe Thea , Shirazi Aida , Weldon Christine B. , Trosman Julia R. , Ravelo Mangalindan Arliene , Liu Raymond
Published: June 2022

e13511

Background: Advance directives (ADs) are an important part of life care planning in patients with cancer. There is a lack of effective interventions that increase AD rates in breast cancer patients prior to surgery. In this quality improvement project, we implemented a 4R Oncology intervention in a community-based cancer center within an integrated health care system. 4R (Right Info / Care / Patient / Time) is a novel care planning and delivery model, which enables patients and care teams to manage complex time-sensitive care with a multi-modality 4R Care Sequence plan, coupled with follow-up workflows. Methods: Patients with newly diagnosed non-metastatic breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at one facility were included in the study. Patients received usual care from 10/1/19 to 9/30/20 (usual care cohort). From 10/1/20 to 9/30/21 (intervention cohort), patients were provided a 4R Care Sequence, which included AD completion prior to surgery, and those without AD were referred for follow-up with a health educator to discuss AD completion. Demographics, NCCN thermometer distress scores, and AD completion rates were compared between the usual care and intervention cohorts using descriptive statistics. Results: Characteristics of age, gender, race/ethnicity, language interpreter usage, Elixhauser Comorbidity Index, NCCN distress scores > 4, surgery type, tumor grade, ER/PR/HER-2 status were similar between the usual care (N=140) and intervention cohorts (N=141). The intervention improved AD completion rates in a time-sensitive fashion prior to surgery between usual care and intervention cohorts, both in total (15% vs 74%, p<.01), and in 3 of the 5 race/ethnicity groups (Table). AD completion rates increased in patients of all races/ethnicities, but increases were not statistically significant for Hispanic patients, likely due to low numbers of these patients in both cohorts. Patients with higher distress scores completed ADs at similar rates to those with lower distress scores. Conclusions: Delivery of 4R Care Sequences, coupled with a health educator follow-up can significantly increase rates of time-sensitive AD completion, regardless of patients’ distress score. Patients across race/ethnicity groups benefited from the intervention, but further efforts are needed to understand the impact of this intervention in patients who are Hispanic. Through an effective care delivery model, patients can be provided with standardized equitable care. [Table: see text]
Globalization of oncology clinical trials: Which lower-middle and upper-middle income countries are participating?
Authors: Rubagumya Fidel , Hopman Wilma M. , Gyawali Bishal , Mukherji Deborah , Hammad Nazik , Pramesh C.S. , Aggarwal Ajay , Sullivan Richard N. , Booth Christopher M.
Published: June 2022

e13512

Background: With globalization of cancer research, many randomized controlled trials (RCTs) led by high income countries (HICs) are now enrolling patients from lower- and upper-middle income countries (LMICs/UMICs). While enrolling diverse global populations promotes research collaborations, there are unanswered questions about which countries participate in RCTs and how this may contribute to global research capacity. Here we describe which UMICs/LMICs participate in RCTs led by HICs. Methods: The study cohort was identified from a database of all oncology RCTs (systemic/surgery/RT) published globally during 2014-2017. The study cohort was restricted to RCTs led by HICs which enrolled participants from LMIC/UMICs. We used a bibliometric approach to explore whether the participation of UMICs/LMICs in RCTs led by HICs was as expected based on other measures of cancer research activity. Country-level bibliometric output for 2007-2017 was identified in the Web of Science database. We compared RCT participation (i.e. % of RCTs in our cohort that each LMIC/UMIC participated in) with country-level cancer research bibliometric output (i.e. % of total cancer research bibliometric output from the same group of countries that came from a specific LMIC/UMIC). Results: The global cohort included 694 RCTs; 636 (92%) of which were led by HICs. Among the HIC-led trials, 187 (29%) enrolled patients in LMICs (n=84) and/or UMICs (n=182); this formed the study cohort. The most common participating LMICs were India (50% of trials, 42/84), Ukraine (46%, 39/84), Philippines (25%, 21/84), and Egypt (14%, 12/84). The most common participating UMICs were Russian Federation (63% of trials, 115/182), Brazil (50%, 91/182), Romania (34%, 61/182), China (31%, 56/182), Mexico (31%,56/182) and South Africa (30%, 54/182). Several LMICs are over-represented in our cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (25% RCTs, 1% output), Georgia (8% RCTs, 0.2% output). Several UMICs are also over-represented in the study cohort of RCTs including Russia (63% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output) and South Africa (30% RCTs, 1% output). The inverse relationship was seen for China (31% RCTs, 69% output). Conclusions: A substantial proportion of RCTs led by HICs enroll patients in LMICs/UMICs. The LMICs/UMICs which participate in these trials are not as one would expected based on overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity strengthening activities require further study.
Cancer care for the poor-health system augmentation model.
Authors: Pendharkar Dinesh , Tripathi Chandramauli
Published: June 2022

e13514

Background: Access to cancer care is well recognized issue. It has many elements, mainly- social inequity, financial, distance to care centers, health behavior etc. These challenges increase with the level of poverty in LMIC. Models of peripheral empowerment, cost reduction, creation of alternate workforce, bending of health systems to include cancer care as a stream are important. Here we report incorporation of cancer vertical in to existing health care delivery models of India (Pendharkar model). Methods: Health care to major population is provided through government lead systems of primary health care centers, merging at district administrative level in to district hospitals. As per various WHO mandates the focus had been on general medicine, surgery, maternal and child health. Through advocacy a parallel vertical of cancer care delivery was initiated, creating “district cancer program” with written down organizational, functional and financial structure. Starting from one state it was expanded to many states. Results: Initiation and launch of district cancer care program has revolutionized cancer care at state level. One medical officer was designated as district cancer nodal officer. He was trained and given physical identity with creation of cancer unit with patient beds, and capacity of performing procedures including chemotherapy. Paramedical personnel and nurses were attached to this unit and trained. Drug formulary of the state was changed with addition of anticancer drugs in to the list. Procurement process at state level was started and units were equipped with anticancer drug bank. Cancer officers were mandated to play various roles like-assist in cancer patients’ journey- from diagnostics to end of life care offering free chemotherapy and palliative care, creating registry, public awareness and professional awareness, assisting in cancer screening programs. The program completing 8 years, has been initiated in 8 states, with nearly 200 districts trained. Five states have formalized it by state notifications issuing operational guidelines with pan state coverage, as a vertical program. Few hundred patients are helped on daily basis. Conclusions: Reduction in cancer care gap can be achieved using existing widespread government health system, by creating vertical cancer program in existing structure. It can be facilitated by utilizing existing resources, capacity building of alternate oncology workforce, mandating health system to take care of cancer patients at affordable cost. [Table: see text]
Practice of antibiotic prophylaxis in patients undergoing mastectomy without immediate reconstruction: A survey of breast surgeons in Pakistan.
Authors: Martins Russell Seth , Shahzad Hania , Masroor Taleaa , Sattar Abida Khalil
Published: June 2022

e13519

Background: Incidence of surgical site infections after breast surgery range from 0.8-26%. Though preoperative antibiotic prophylaxis (AP) is widely used, international and national guidelines lack focus on post-operative antibiotic prophylaxis (PAP). This survey of surgeons in Pakistan reports surgeon preference for AP in cases of mastectomy without immediate reconstruction but with indwelling drains. Methods: An anonymous, online, validated 16-item survey, exploring peri-operative antibiotic choices and prescribing practices was disseminated to a working-group of 30 leading breast surgeons in Pakistan. Descriptive statistics were performed using Statistical Package for Social Sciences (SPSS) version 21. Results: A total of 25 (response rate: 83.3%) members responded, with the majority being fellowship-trained breast surgeons/surgical oncologists (68%) and having > 10 years’ experience (60%). For mastectomy without reconstruction, though most (76%) reported routine use of pre-operative AP, there was considerable variation in post-operative AP. 36% reported no further AP after a single dose of pre-operative AP, 24% continued AP for 24 hours in high-risk patients only, while 24% continued AP for 24 hours in all patients. 12% continued post-operative AP in all patients for 7 days, while 4% reported continuing post-operative AP for the duration of indwelling drains. Antibiotic choice for peri-operative AP also varied. 56% used cephalosporins, 24% used penicillin, and the remaining 20% reported that their choice varied across patients. Conclusions: There is widespread variation in surgeon comfort with discontinuation of AP after the first pre-operative dose in patients undergoing mastectomy without immediate reconstruction but with indwelling drains. Large randomized controlled trials are necessary to develop guidelines to ensure uniformity and evidence-based post-operative AP.
Breast cancer in young women in Guatemala: A retrospective comparative cohort study.
Authors: Kihn-Alarcón Alba , de Falla Vicky , Siliézar Mauricio , Orozco Loida Isabel , García Carlos , Figueroa Javier , Ruiz Edgar , Toledo-Ponce María Fernanda , García-Rivera Mariluna , Dávila Sonia , Sobrevilla Liliana , Henke Lauren E , Gay Hiram Alberto , Van Rheenen Jacaranda , Velarde Angel
Published: June 2022

e13523

Background: In Guatemala, breast cancer is the most common malignancy among women, the socioeconomic variability among the population directly affects the access to screening and treatment, and little is known about the behavior of the disease among younger women, reason why the aim of our study is to describe the clinico-pathological characteristics in this population. Methods: Retrospective study performed of patients with a confirmed biopsy of breast cancer that were treated at Liga Nacional Contra el Cáncer - INCAN in Guatemala, the largest cancer center in the country. From medical records, we obtained: clinico-pathological and treatment (surgery, radiotherapy, endocrine therapy) data and compared results between ≤40 years and >40 years old women. Results: The study identified 1,347 patients, 190 (16.42%) ≤40 years old women and 1,157 (83.57%) >40 years old. The mean age at diagnosis among patients was 36 vs. 56 years old, respectively (p<0.01). According to our findings, even though most patients came from the region I of the country that is the capital city, there was a higher percentage of patients from the West regions (VI, VII) that belonged to the younger group 22.22% vs 10.58%. Furthermore, 74.4% of ≤40 years old patients were staged as locally advanced or metastatic vs >40 year old patients (48.04%), and 65.34% of ≤40 years old were found to have triple negative and Her2 enriched subtypes vs 46.13% in >40 years old (p<0.01). Conclusions: Young breast cancer patients in Guatemala are characterized by being diagnosed at locally advanced and advanced stages of the disease with more biologically aggressive subtypes such as triple negative and her2 enriched. [Table: see text]
Canadian medical oncology workforce and cancer incidence trends: Supply and proxy demand analyses from 1994 to 2020.
Authors: Fundytus Adam Michael , Loewen Shaun , Easaw Jacob , Yip Steven , Hao Desiree
Published: June 2022

e13526

Background: It is unclear whether the Canadian medical oncology workforce has kept pace with the country’s rising cancer incidence over the last three decades. This study sought to characterize the national and provincial trends in the medical oncologist (MO) and MO trainee workforce during the last 27 years and explore the relationship between workforce and cancer incidence. Methods: Publicly available databases from the Canadian Medical Association (CMA; 1994-2019) and Canadian Institute of Health Information (CIHI) database (1994-2020) were utilized to estimate the number, demographics, and regional distribution of practicing MOs in Canada from 1994 to 2020. Cancer incidence by province was obtained from Statistics Canada for the period 1990 to 2018, except for Quebec where only 1990-2010 data was available, and then projected to 2020 across five regions (The West Coast, The Prairies, Ontario, Quebec and Atlantic Canada) using Canadian population statistics from Statistics Canada and age-period-cohort modeling. To estimate changes in demand for, and supply of, medical oncology services over time, annual cancer incidence to MO provider ratios were calculated. Finally, the Canadian Post MD Education Registry (CAPER) database (1994-2020) was used to characterize the number of MO trainees. Results: Between 1994 and 2020, annual cancer incidence nationally rose from 120,255 cases to 225,800 cases (88%), while the number of MOs increased from 161 to 642 (298%). Incident cancer cases to medical oncologist (MO) ratio dropped from 749:1 in 1994 to 352:1 in 2020. This ratio fell in all five analyzed regions from 1994 to 2020 (Atlantic Canada 1836:1 to 447:1, The Prairies 1257:1 to 377:1, The West Coast 909 to 261:1, Ontario 682:1 to 411:1 and Quebec 543:1 to 300:1). In 1994, 24% of MO providers were ≥ 50 years old compared with 40% in 2020. Nationally, the MO workforce has nearly reached gender parity with 46% female in 2020 versus 25% in 1994. Trends in Canadian MO trainees have largely mirrored MO trends with a 203% increase in the annual trainee cohort from 34 in 1994 to 103 in 2020. In 1994, 34% of trainees were female compared with 63% in 2020. The largest proportion of the country's MOs (34% in 2020) and MO trainees (49%) are located in Canada’s most populous province, Ontario. Conclusions: Although the Canadian MO workforce has shown considerable growth between 1994-2020, a higher proportion of MO providers are nearing retirement age and may influence future workforce trends. Moreover, our study was not able to take into consideration referral patterns or the increasing number and complexity of systemic therapies that also influence MO workload. Ongoing monitoring of human resource levels in medical oncology and cancer incidence data are key metrics to meaningfully inform MO training programs of an appropriately sized trainee cohort and ensure future demands for MO services in cancer care are met.
Hospitalization rate differences among cancer patients on biologics and biosimilars.
Authors: Reddy Shirisha , Rutter Wilbur , Cavers William , Avalos-Reyes Elisea , Johnson Kjel Andrew
Published: June 2022

e13530

Background: Febrile neutropenia (FN), a severe adverse effect of many cancer treatments, often results in emergency hospitalizations. Granulocyte colony-stimulating factors (G-CSF; filgrastim and pegfilgrastim) have proven efficacy in the prophylaxis of chemotherapy-induced neutropenia and are associated with reducing FN and hospitalizations. Clinical studies have shown that biosimilars are comparable to their originator products; however, no real-world studies on the impact of biosimilar G-CSF on FN hospitalizations exist. We hypothesize that no difference in FN-related hospitalizations between biosimilar and originator biologic G-CSF will occur. Methods: This was a retrospective cohort study of adult patients receiving either biologic G-CSF or biosimilar G-CSF from 5/1/2018 through 4/30/2021. Patients were followed from their initial G-CSF fill during the study period until 30 days following the last dose received. Patients were excluded if they switched exposure groups during the study period or did not maintain eligibility for the duration of follow-up. The primary outcome was FN hospital admission rate between the two groups, defined as any inpatient claims with the primary diagnosis ICD-10 code D70.1 or R50.2. Descriptive statistics and logistic regression were conducted to account for confounding between the groups. Incidence rates were calculated per 1000 person-years of exposure (PY); p-values < 0.05 were considered significant. Results: A total of 13,670 patients met the inclusion criteria, with 6,939 (50.8%) receiving biologic G-CSF. Biosimilar patients were younger (Mean [standard deviation (SD)]: 63.8 [13.4] vs. 65.5 [13.0] p < 0.05), male (40.0% vs. 37.2%; p < 0.05), had more G-CSF claims (Mean [SD]: 5.6 [6.8] vs. 4.5 [4.3]; p < 0.05) and were more likely to utilize a specialty pharmacy (10.1% vs. 4.7%; p < 0.05). Pegfilgrastim was the most common G-CSF medication overall (73.5%); however, filgrastim use was significantly more common in biosimilar patients (43.2% vs. 10.4%; p < 0.05). FN hospitalizations were rare, with 1.1% of patients experiencing an event. No difference in hospitalizations were noted (biosimilars: 1.1%, biologics: 1.0%; p = 0.39). After regression, no factors analyzed were associated with FN-related hospitalizations. Crude FN incidence rates were 45.9 cases per 1000 PY (95% Confidence Interval [CI]: 35.6-56.1 per 1000 PY) among biosimilar patients compared to 37.5 cases per 1000 PY (95% CI: 28.6-46.4 per 1000 PY) among biologic patients, resulting in a rate difference of 8.3 cases per 1000 PY (95% CI: 5.2-22.0 cases per 1000 PY; p = 0.22). Conclusions: In a large real-world analysis, biosimilar G-CSF demonstrated similar effectiveness in preventing FN hospitalization as originator biologic G-CSF agents.
Survival trends in hilar and extrahepatic cholangiocarcinoma based on Facility type: A National Cancer Database analysis.
Authors: Abodunrin Faith , Eyitemi Joshua , Jain Shalini , Tupper Connor , Silberstein Peter T. , Eaton Vincent
Published: June 2022

e13536

Background: The diagnosis and treatment of Cholangiocarcinoma continues to pose a challenge. Due to their rarity, few studies have examined the impact of facility type on the survival of patients with extrahepatic cholangiocarcinoma. The hypothesis of this study was that differences in the outcome of patients at different facility types exist. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with hilar and extra-hepatic cholangiocarcinoma from 2004 to 2017 using ICD-O-3 histology codes. We used four different cohorts to assess survival amongst those at different facility types: academic/research programs, community cancer programs, comprehensive community center programs, and integrated network cancer programs. Data was analyzed and descriptive statistics and Kaplan Meier curves were produced using SPSS to measure survival in these patients with statistical significance set at α = 0.05. Results: Using the database, a total of 57,146 patients with hilar and extrahepatic cholangiocarcinoma were identified. Overall median survival in these patients was 11.2 months. Patients at Academic/research programs had a median survival of 14 months (95% CI 14.1-14.8 p < 0.001). In comparison, median survival of 9.7 months (95%CI 9.3-10.2 p < 0.001) and 8.7 months (95% CI 8.4-8.9 p < 0.001) was noted in Integrated network and Comprehensive community cancer programs, respectively. Community cancer programs had the lowest median survival rate in patients with all extrahepatic biliary tract cancers included in our study was 6.9 months (95% CI 6.4-7.7 p < 0.001). Specifically, patients with Klatskin tumors at Academic/Research programs had median survival of 10.3 months (95% CI 8.6-11.9 p < 0.0010) compared to median survival of 3.6 months in patients treated at Community Cancer program. We also studied specific histology types such as papillary and mucinous adenocarcinomas. In papillary adenocarcinomas, there are no statistically significant differences in median survival in different facility types. In mucinous adenocarcinomas, median survival of 26.5 months was found in academic/research program patients compared to 16.2 months in Comprehensive Community Cancer program patients (p < 0.001). Conclusions: Median overall survival in patients with hilar and extrahepatic cholangiocarcinoma was significantly higher in academic/research programs compared to other facility types. Further studies are needed to ascertain why academic/research programs have superior outcomes in these patients.
A novel clinical trials imaging network platform for RECIST 1.1, and related protocols run on standard radiology software: A pilot at multiple oncology centers.
Authors: Goldstein Don , Hochster Howard S. , Malhotra Jyoti , Goldszal Alberto , Sokol Levi
Published: June 2022

e13552

Background: Oncologists face the following challenges with clinical trials imaging analysis: non-structured radiology reports, inconsistent lesion measurement between time points, time-consuming and error-prone manual calculations for clinical trials protocols, and lack of dedicated storage and auditable signoff. Clinical Trials Imaging Network (CTIN) is a novel clinical trials imaging platform that allows radiologists to provide oncologists with dedicated clinical trials imaging reads and calculations from non-proprietary standard radiology dictation and PACS software, using RECIST 1.1 and other tumor response criteria. It was piloted at several cancer centers between 2019 and 2021. Methods: An anonymous survey was sent out to the oncologist and research coordinators who have experience using the CTIN program. The survey was designed to gauge the effectiveness of the software. Questions asked included the decrease in turnaround time between initiation of scan and completion of research protocol calculations, and regarding the decrease in time the oncologists personally need to make calculations. Additionally, respondents were inquired regarding the accuracy of the data, and how much time they had to spend verifying the integrity of the data. Results: The survey was sent to approximately 150 recipients, with 32 respondents. 84.4% of respondents said they strongly agreed or agreed that there was a decreased turnaround time between scan initiation, and completion of research protocol calculations, and 15.6% neither agreed nor disagreed. 80% strongly agreed or agreed that there was a decreased time they personally performed the calculations. 25.0% said they saved less than 5 minutes per time point personally performing the calculations, 28.6% said 5-15 minutes, 23.4% 15 to 30 minutes, and 17.8% 30-60 minutes. Users were also asked regarding their time spend verifying the data. 64.5% of people spent less than 5 minutes per time point verifying the integrity and quality of the data. 19.4% spent 5-15 minutes, 12.9% spent 15-30 minutes, and 3.2% 30-60 minutes. No one spent greater than 60 minutes verifying the data. 65.6% of people strongly agreed that they were confident in the accuracy of the data, 25.0% agreed, and 9.4% neither agreed or disagreed. 90.6% of people said that they were very satisfied or satisfied with CTIN. Conclusions: We have piloted an approach to provide clinical trials imaging metrics to oncologists using non-proprietary technology that runs from any standard radiology voice recognition system and PACS. The majority of respondents agreed that they would recommend this system for its time-saving, automated calculation and ease of use, user features. The CTIN platform bridges the gap between general radiology reads and clinical trials imaging reads without the need for dedicated radiology software.
ENLIGHT: Pancancer response prediction to targeted and immunotherapies via tumor transcriptomics.
Authors: Aharonov Ranit , Dinstag Gal , Shulman Eldad , Elis Efrat , Ben-Zvi Doreen , Tirosh Omer , Hoang Danh-Tai , SInha Sanju , Apolo Andrea B. , Dahut William L. , Lipkowitz Stan , Berger Raanan , Kurzrock Razelle , Papanicolau-Sengos Antonios , Karzai Fatima , Rajagopal Padma Sheila , Gilbert Mark R. , Aldape Kenneth D. , Beker Tuvik , Ruppin Eytan
Published: June 2022

e13556

Background: Precision oncology is gradually advancing into mainstream clinical practice. Despite the significant recent growth in the number of approved biomarkers for immune and targeted therapies, demonstrating significant survival benefits, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers. Methods: We developed ENLIGHT - a transcriptomics-based computational platform that identifies and utilizes clinically relevant genetic interactions (GIs) to predict a patient’s response to cancer treatments. ENLIGHT markedly extends and improves upon SELECT, a previous GI-based framework for obtaining transcriptomics-based response biomarkers. In this study, we focus on three key translational aspects: (i) the number of drugs for which predictions can be obtained (ii) defining a biomarker-based test for Personalized Medicine (PM) that would identify favorable treatments for an individual; and (iii) Improving clinical trial design by excluding a sub-population of patients likely not to respond to the treatment. A key translational feature of the approach is that it does not require training on treatment response data. Thus, in addition to its ability to predict patients' response to approved and well-studied therapies, it can predict the response to new, unexplored treatments. Results: We first tested Enlight in the PM scenario, analyzing 21 patient cohorts from diverse indications, treated with a variety of targeted and immunotherapies. The ENLIGHT treatment matching score is associated with better response with an aggregate Odds Ratio (OR) of 2.59 (95% confidence interval [1.85, 3.55], p= 3.41 e-8). Applied to the WINTHER trial data, encompassing multiple indications and individualized treatments, ENLIGHT recommendations achieved a highly remarkable OR of 11.15 ([2.3, 54.5], p = 8 e-04), demonstrating ENLIGHT’s strong predictive power across a broad spectrum of treatments and cancer types. Second, using ENLIGHT to exclude patients from clinical trials increases the trial response rate, achieving more than 90% of the response rate attainable under an optimal exclusion strategy. Conclusions: ENLIGHT is a powerful transcriptomics-based precision oncology pipeline developed by Pangea Biomed that broadly predicts response to both extant and novel targeted and immune therapies in translationally oriented, clinical terms, going beyond case-specific biomarkers.