bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational relevance of HER2-low expression in triple-negative breast cancer: A retrospective single-center study.
Authors: Mufti Suhail Sayeed , Sanghavi Niyati , Ramaswamy Veena , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah
Published: June 2022

e13061

Background: In current clinical practice, the decision of using anti-HER2 targeted agents for breast cancer is based primarily on HER2 protein overexpression, assessed using immunohistochemistry and/or HER2 gene amplification on FISH assay(2018 ASCO/CAP guidelines). It is increasingly being recognized that HER2-negative breast cancer is characterized by a wide spectrum of HER2 expression, particularly important for the triple-negative breast cancer (TNBC) group, the treatment options for which are far less compared to hormone receptor-positive tumors. HER2-low breast cancer (HER1+ or 2+, without gene amplification) is an emerging subtype with differing clinicopathologic and prognostic implications. There is accumulating evidence that HER2-negative tumors may switch to HER2-low status and vice versa at tumor recurrence. The development of newer drug classes like antibody-drug conjugates and immunotherapy have created a window of opportunity for this sub-category of breast cancer. Methods: We aimed to evaluate HER2 0/normal and HER2-low expression in TNBCs, their clinicopathological characteristics, and prognostic significance. Clinical and laboratory data for 207 TNBC cases (184 non-metastatic and 23 metastatic) diagnosed between February 2010 and December 2019 was available for analysis and cases were followed up until December 2021. Androgen receptor (AR) immunohistochemistry was performed on available FFPE blocks. Results: Non-metastatic TNBCs: Median age was 50 (SD 11.77; range 23 to 82) years. 91.9% of HER2-low cases were more than 40years old compared to 70.1% of HER2 0 cases, p = 0.006. 79.9% were HER2 0, 14.1% were HER2 1+, and 6% were HER2 2+. 30.7% (39/127) of cases were AR+. Compared with HER2 0, HER2-low cases exhibited a lower histological grade (Her2 0 - Grade 3: 72.7%, Grade 2: 27.3%; Her2-low- Grade 3: 57.1%, Grade 2: 40%, Grade 1: 2.9% p=0.048). Compared with HER2 0, more of HER2-low cases were AR+ (For Her2 0 26.5% were AR+; For Her2-low 48% were AR+, p=0.036). There was no significant difference in disease-free survival between the two groups. There was no significant difference in overall survival (OS) between the two groups (Her2 0- Mean: 102.0 months, Median: Not achieved; Her2-low - Mean: 69.60 months, Median: 77.4 months p=0.73). Within the Her2-low group, patients ≤40 years had a median OS of 44.3 months. Metastatic TNBCs: Median age was 47 (SD 10.38; range 30 to 74) years. There was no significant correlation between the clinicopathological characteristics. No significant difference in OS was seen (Her2 0- Median: 44.9 months; Her2-low- Median: 24.3 months, p=0.20). Conclusions: The non-significant trend towards a lower survival for Her2-low TNBCs, coupled with a surprisingly lower histologic grade and a higher AR positivity needs to be further evaluated in larger studies. Further translational research to optimize treatment for this subgroup is needed.
Phase I trial combining pembrolizumab and doxorubicin in patients with metastatic triple negative breast cancer.
Authors: Yuan Yuan , Ge Xuan , Yost Susan Elaine , Lee Jin Sun , Frankel Paul Henry , Ruel Christopher , Cui Yujie , Murga Mireya , Tang Aileen , Martinez Norma , Karimi Misagh , Somlo George , Mortimer Joanne E. , Waisman James Ross
Published: June 2022

e13071

Background: Pembrolizumab (pembro) in combination with chemotherapy (chemo) has recently become standard of care in patients with programmed death-ligand 1 (PD-L1) positive metastatic triple negative breast cancer (mTNBC). Optimal chemo partner with pembro remains debatable. The current phase I study evaluated the safety and efficacy of doxorubicin (dox) + pembro in anthracycline-naïve mTNBC patients (NCT02648477). Methods: Patients with mTNBC, no prior anthracycline, and ≤2 lines of prior chemo for metastatic disease were enrolled. Patients received pembro 200mg IV and 50-60 mg/m2 dox IV every 3 weeks x6, followed by pembro maintenance until progression or unacceptable toxicity. The primary objectives were safety and objective response rate (ORR per RECIST 1.1). For the safety lead-in, we employed a 3-at-risk rolling design. Results: Ten patients were accrued between March 2016 and November 2019. The trial stopped early due to poor accrual. The first 3 patients received dox at 50mg/m2 without dose limiting toxicities and dose was escalated to 60mg/m2 for the remaining patients. Median age was 62 years (range 41-87). Grade ≥ 3 AEs were: 4 neutropenia, 2 dyspnea, 2 fatigue, 1 oral mucositis, 1 hyponatremia, 1 acidosis, 1 alkalosis, 1 hypotension and 1 respiratory failure. One patient (age 87) received 1 dose of therapy, developed neutropenia and respiratory failure which led to death, and was not eligible for response assessment. 1 patient did not have RECIST measurable disease. Two patients had dose delay (1 G3 neutropenia and 1 G2 upper airway infection). 1 patient had dose reduction due to G3 fatigue. Immune toxicity was consistent with known pembro toxicity. Of 9 evaluable patients, responses were : 1 CR, 3 PR, 2 UPR, 2 SD and 1 PD, which translated to a best ORR of 67% (95% CI, 13.7%, 78.8%). CBR at 6 mo was 56% (95% CI 21.2%, 86.3%). Median follow-up time was 34.6 mo (range 14.5 - 45.4 mo). Median PFS was 5.2 mo (95% CI 4.7, NA); and median OS was 15.6 mo (95% CI 13.3, NA). Eight patients had PD-L1 (22C3) testing: 4 positive and 4 negative. No association between the PD-L1 status and response was observed. Conclusions: The combination of pembro+dox was well tolerated and had modest activity in anthracycline-naïve patients with mTNBC. The finding needs to be further confirmed with future study. Clinical trial information: NCT02648477.
Characteristics of disease course in patients with locally advanced primarily inoperable HER2-negative breast cancer.
Authors: Samaneva Natalia Yu. , Vladimirova Liubov Yu , Storozhakova Anna E. , Kalabanova Elena A. , Kabanov Sergey N. , Tishina Anna V. , Gaysultanova Yakha S. , Teplyakova Maria A. , Lyanova Aza A. , Abramova Natalia A. , Ryadinskaya Ludmila A. , Udalenkova Irina A. , Tikhanovskaya Natalia M. , Popova Irina L. , Sergeeva Marina M. , Vashchenko Larisa N.
Published: June 2022

e13072

Background: Breast cancer (BC) is the most common cancer in women worldwide. The purpose of the study was to analyze immediate and long-term results of treatment in patients with locally advanced primarily inoperable HER2-negative breast cancer depending on the time of progression. Methods: The study included 104 women with locally advanced primarily inoperable HER2-negative breast cancer who developed an early disease progression within 6 to 12 months after standard combination treatment. The blood levels of circulating tumor cells (CTCs) were measured in all patients during the progression stage. Results: An analysis of the overall (OS) and event-free (EFS) survival showed that median EFS in patients with luminal B subtype was 9 months, in patients with triple-negative (TNBC) subtype 8 months. EFS at 6 months was 87.5% in luminal B subtype and 79.4% in TNBC, p = 0.37985. Median OS in patients with luminal B subtype was 25 months, in patients with TNBC 26 months. One-year OS was 100% in luminal B subtype and 93.9% in TNBC, p = 0.138. 2-year OS was 54.2% in luminal B subtype and 55.9% in TNBC, p = 0.697. 3-year OS was 37.5% in luminal B subtype and 41.2% in TNBC, p = 0.639. CTCs were detected in all patients, with higher levels in patients with luminal B subtype than in TNBC patients. HER+ CTCs were found in 30% of patients with luminal B subtype but not registered in patients with TNBC. Such results were obtained for the first time. Conclusions: The absence of significant differences demonstrated the aggressive disease course in patients with luminal BC with identified primary hormone resistance, similar to the TNBC course. The results should be taken into account when predicting the course of the disease and developing further treatment tactics.
The effects of bone targeted therapy in patients with greater than two years survival with metastatic breast cancer and bone metastasis.
Authors: Jayan Athira , Raghavendra Akshara Singareeka , Bassett Roland L. , Barcenas Carlos Hernando
Published: June 2022

e13076

Background: Administration of bone targeted therapy such as zoledronic acid (ZA) or of denosumab (D) decrease the risk of skeletal related events (SRE) such as radiation to the bone, pathological bone fractures, and spinal cord compression in patients with a diagnosis of metastatic breast cancer (MBC) and bone metastasis. As these patients continue to live longer it is unknown what are the impacts from long-term administration of ZA or D among those who live longer than 2 years. Methods: This was a retrospective analysis of patients with MBC and bone metastasis who lived for more than 2 years since diagnosis and received treatment at MD Anderson Cancer Center for MBC in addition to ZA and/or D between 2015 and 2021. Patient demographics, date of diagnosis, tumor characteristics, bone targeted agent treatment plans and SRE were extracted from the institutional database and electronic health records. We defined 3 patterns of receipt of bone targeted therapy: Pattern A: ZA every 3-4 weeks; Pattern B: D every 4-6 weeks; Pattern C; D every 4-6 weeks for a period followed by every 3 months. The association between these patterns and SRE was assessed using Fisher’s exact test. Results: We included 178 patients: Pattern A with 49 patients, Pattern B with 85 patients, and Pattern C with 44 patients. The proportion of patients who suffered a SRE in Patterns A, B, and C were 22.4% (11/49), 20% (17/85), and 21.4% (10/44). There was no statistical difference in the proportion of SRE between these three groups (p = 0.92). Conclusions: We did not observe a difference in the rate of SRE between the three different patterns of bone targeted therapy administration in patients with MBC and bone metastasis. Other treatment patterns will be considered in future analysis.[Table: see text]
Evaluating efficacy on tumor biopsy tissue ex vivo before treatment for equitable cancer care.
Authors: Patel Heli K. , Punjani Zeenia , Charania Areesha A. , Patel Zeelu H. , Papachristou Georgios , Contreras Carlo M. , Tsung Allan , Budhwani Karim I.
Published: June 2022

e13502

Background: Nearly half the world will be diagnosed with cancer. Each year, > 1.7 million new cancers are diagnosed in the US. Worse, systemic therapy turns out to be ineffective in 70% of patients because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. Each tumor’s distinct composition and heterogeneity can result in diverse responses to the same treatment. There is a critical and urgent need to develop ex vivo personalized cancer models that match patients with the right treatment – before treatment. Here we present a low-cost ex vivo personalized cancer model to rapidly evaluate effectiveness of various therapeutics on intact core biopsy tissue obtained from a patient’s tumor. Objective: The goal of this study is to deliver multiple isolated fluid streams to spatially distinct regions (SDRs) of intact core biopsy specimens for evaluating efficacy of multiple anticancer agents simultaneously. Methods: Core biopsies were generated from xenograft and resected human tumor tissue using 18-gauge and 20-gauge spring-loaded biopsy systems. Xenografts were established using cell lines with known sensitivity and resistance profiles. Fluid streams with anticancer agents, nucleic acid stains, and mock drugs were delivered to spatially distinct regions (SDRs) on intact core biopsy specimens in our patented Personalized Oncology Efficacy Test (POET) lab-chip bioreactors. High content imaging and custom image processing algorithms were used to measure differential activity. Results: No lateral fluid surface conduction, and only minimal lateral diffusion, was observed up to 200 μm deep in tissue. Extent of observed lateral diffusion was within operational parameters of the bioreactor. Integrity of spatially distinct regions on intact core tissue was maintained. Differential activity from anticancer agents compared to mock drugs was observed and quantitatively measured using custom image processing algorithms. Conclusions: The NCI warns that “current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate.” A personalized medicine approach, based on efficacy observed on tissue directly from the patient’s own tumor, is fundamentally better than the current approach. Low-cost next generation ex vivo cancer models that can rapidly match treatments to tumors, such as POET, could transform cancer treatment and make a significant impact on the lives of patients.
Democratizing cancer innovation by reducing cost and complexity of cancer models.
Authors: Punjani Zeenia , Patel Zeelu H. , Charania Areesha A. , Patel Heli K. , Papachristou Georgios , Contreras Carlo M. , Tsung Allan , Budhwani Karim I.
Published: June 2022

e13503

Background: Despite advances in high-throughput screening, combinatorial chemistry, databanks, and computational models, drug R&D remains expensive and slow, often over a decade. It is estimated that pre-human costs are > 30% of cost of approved drugs: $1.5 billion of $3.9 billion. Another study estimates that pharma spends $34.4 billion annually on preclinical research. However, 90% of drugs effective in pre-human studies fail in human trials. A reason for this dissonance is the inadequacy of current assays and methods for evaluating efficacy of new treatments during preclinical evaluation. Cell culture dishes fail to recapitulate the in vivo microenvironment, making cells far from physiologically relevant. Animal models, though physiologically relevant, are limited indicators of success in subsequent human trials. Predicting which preclinical formulations will most likely succeed in clinical trials, by matching them against patient biopsy specimens, could reduce cost and time-to-market of new therapeutics. Objective: The aim of this study is to develop an ex vivo cancer model that can predict clinical success of preclinical formulations by screening efficacy on live patient biopsy tissue. Methods: Softlithography with SU-8 photoresist and polydimethylsiloxane (PDMS) was used to fabricate microporous thin membranes with uniform porosity. Electrospinning with collagen and Nylon was used for fabricating nanofibrous membranes with well-interconnected, non-woven, non-uniform porosity. Multicellular biomimetic healthy and tumorous microtissue was cultured with pancreatic and colorectal cell lines. Permeability assays were used to validate barrier and transport functions, scanning electron microscopy was used to validate morphology, and fluorescent and confocal microscopy were used to observe migration, invasion, and metastasis. Results: Permeability assay confirmed transport and barrier functions wherein small molecules (10 kDa) diffused while larger molecules (500 kDa) were prevented from flowing. Migration and invasion were observed when microfluidic circuits connected S2VP10-Luc “tumorous” tissue upstream from “healthy” vascular and muscle tissue. Moreover, subpopulations of invasive cells showed a more aggressive proliferation profile compared to subpopulations of the same cell-line cancer cells that remained at the original “tumorous” site. Conclusions: Microfluidic ex vivo cancer models have the potential to transform cancer treatment from bench – as clinical trial simulation tools to narrow down lead and backup candidates – to bedside – as predictive personalized companion diagnostics to guide treatment strategy – along the drug discovery to market roadmap for novel therapeutic agents.
International consensus guideline for anticancer drug dosing in kidney dysfunction (ADDIKD): A standardized approach to assessing kidney function in cancer patients and its application to anticancer drug dosing.
Authors: Sandhu Geeta , Adattini Josephine , O'Neill Niamh , Armstrong Gordon Evangeline , Kelly Aisling , Shingleton Julia , Liauw Winston S. , Ward Robyn L. ,   Working Group for the International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction
Published: June 2022

e13518

Background: Anticancer drug dosing recommendations in kidney dysfunction are often empirical, based on non-standardised creatinine assays calculated via the Cockcroft-Gault equation, and lack applicability to globally accepted kidney dysfunction classifications. ADDIKD aims to provide a standardised approach to assessing kidney function in cancer patients, and to apply evidence and consensus-based recommendations to anticancer drug dosing in kidney dysfunction. Methods: An expert international multidisciplinary working group was established to develop anticancer drug dosing recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to critically appraise the quality and strength of evidence and formulate recommendations. The working group participated in workshops to achieve > 80% consensus for a standardised approach to assessing and classifying levels of kidney function, its application to anticancer drug dosing in kidney dysfunction, and dosing recommendations for individual drugs. Upcoming public consultation will refine these recommendations and facilitate acceptance as an international benchmark. Results: Three key recommendations formed the basis of ADDIKD: Application of estimated glomerular filtration rate via the Chronic Kidney Disease-Epidemiology Collaboration equation (eGFRCKD-EPI) to guide the assessment of kidney function, except where directly measured glomerular filtration rate (mGFR) is clinically necessary. Where the anticancer drug dose is dependent on kidney function and mGFR is not clinically necessary, eGFRCKD-EPI is suggested to guide dosing. Application of the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease categories to guide stepwise dose adjustments of anticancer drugs in kidney dysfunction. A review of 2263 published articles and 177 registered product information monographs enabled 127 GRADE assessments by the working party, resulting in evidence and consensus-based dosing recommendations for 59 anticancer drugs. 'Quick reference’ dosing tables incorporated a traffic light system for alerting clinicians to caution around levels of kidney function and specific patient risk factors for consideration. Conclusions: eGFRCKD-EPI is the most accurate and convenient method for assessing kidney function in diverse populations (including cancer patients) and accounts for the standardisation of the creatinine assay. ADDIKD’s expert acceptance of this standardised approach, together with anticancer drug dosing recommendations in kidney dysfunction, provides a practical tool to establish clinically relevant dosing in this patient population.
Relationship between race and anemia in women undergoing surgery for gynecologic cancer.
Authors: Cain Abigail , Galvan-Turner Valerie Bianca
Published: June 2022

e13529

Background: Anemia is associated with poor outcomes after gynecologic surgery and there is a paucity of data whether race modify its impact on outcome. The goal of this study is to estimate the anemia prevalence in women undergoing surgery for gynecologic cancer and to evaluate the relationship between preoperative anemia and postoperative morbidity and understand whether race and ethnicity modify this relationship. Methods: We performed a retrospective cohort study of patient’s undergoing surgery for a gynecologic malignancy between 2014 and 2019 using data from the National Surgical Quality Improvement Program. Multivariable logistic regression was used to determine adjusted odds for post operative morbidity with anemia. Interaction terms were entered into the model to test for effect modification by race and ethnicity. Results: We found that Black women were twice as likely to suffer from anemia then Caucasian women. In Caucasian women 79% had normal Hgb level, 16% mild anemia, 5% moderate anemia, and 0.5% with severe anemia. However, in Black women only 59% had normal Hgb level, with 30% having mild anemia, 10% moderate anemia, and 1% with severe anemia. We also found that the adjusted odds ratio of postoperative morbidity was higher in Black women with moderate and severe anemia than in Caucasian women. (Table). Logistic regression models to predict the probability of mortality for women with varying stages of anemia. Showing a difference in probability of morbidity between Black women and Caucasian women of undergoing gynecologic oncologic surgery. Conclusions: In this cohort of 56,240 patients who had surgery for a gynecologic malignancy we found that 24% had anemia. when treated may improve postoperative outcomes were more likely to have anemia than Caucasian women in this cohort. Black women had higher rates of postoperative morbidity at all levels of anemia, demonstrating continued disparities in care. Preoperative anemia is a modifiable risk factor that when treated may improve postoperative outcomes.[Table: see text]
Sequential EHR-based dynamic graph network for multiple myeloma detection and feature interaction investigation.
Authors: Wei Guanhao , Zhou Li , Lu Lynn L. , Romano Marc
Published: June 2022

e13591

Background: Electronic Health Records (EHR) provide the possibility of leveraging modern machine learning algorithms for disease detection prediction. Since a patient’s medical journey contains a complex pattern and it is difficult to identify interactive feature impacts, we propose to reconstruct patients’ attributes at different time points into dynamic graphs. Then we can use graph-based learning algorithms to enhance the predictive precision and identify leading feature interactions that reveal key services transitions. Methods: Sequential EHR like diagnosis (Dx), procedure (Px) and prescription (Rx) can be transformed into dynamic temporal graphs with nodes representing attributes, services, and medical status and edges representing patient-object interactions. Also, graph based sequential recommendation can use structured historical behavior trajectories as input, aiming to predict patient’s next behavior. Then, the model can investigate patients’ time-sensitive features interactively identifying a potential disease and then output a probability of getting that disease. Dynamic graphs can also help to track patient’s medical treatment/drug use service transitions. Results: We applied our method on a Newly Diagnosed Multiple Myeloma (NDMM) dataset consisting of 1.5 million candidates’ longitudinal medical claims from 2017 to 2020 with diagnosis rate around 0.6%. In this data set, patients’159 aggregated Dx, Rx and Px features, together with 30 demographic attributes are updated monthly. The model was trained on 4 monthly data cohorts from the 12/2017 to 03/2019 period and its performance was tested on 9 monthly cohorts from year 2020. The 1000 patients scored as having highest risk were evaluated for the predictive precision which was around 6.5% This precision compares most favorably relative to the reported 0.76% lifetime risk of getting multiple myeloma in US. We also captured the top, service transitions in NDMM patients having 30% more frequency than those in overall populations. Conclusions: The novel dynamic graph-based learning approach on a large-scale EHR dataset demonstrates the advancement of the disease detection methodology. While the outcome of this model significantly improves the accuracy of predictive precision, it also helps identify more meaningful key drivers attributing to disease. The incremental new patients identified through this novel model will provide a better basis for the evolving identification solution within Biopharma industry.
The use of ARMCan app to improve the quality of life in breast cancer patients with chemobrain.
Authors: Koehler Abigail N. , Rothman Yehudit , Gomez Enriquez Diego , Kirschner Michelle , Shatz Rhonna , Mahammedi Abdelkader , Rebola Claudia B. , Sengupta Soma
Published: June 2022

e13619

Background: Breast cancer is the most diagnosed cancer in women with approximately 2 million women diagnosed in 2018. The 10-year survival rate is 78%. Breast cancer patients who undergo chemotherapy treatment can suffer neurocognitive impairment resulting in significant effects on their cognitive functioning. Chemotherapy-related dysfunction is known as “chemobrain”. Chemobrain is the basis of significant neurological morbidities in the breast cancer population. It causes difficulty in people being able to carry out activities of daily living and impacts people’s livelihoods and well-being. Studies have shown that music-based intervention can improve cognitive function. Methods: Since music-based interventions to specifically address chemo-related cognitive deficits have not been explored, we are conducting a pilot feasibility study to beta test the novel Active Receptive Music for Cancer patients application (ARMCan) which allows its user to have an interactive musical experience. Patients are randomized into two arms. In receptive listening, users listen to a genre of their choice, and in active listening, users add sounds over a base trace. At the beginning of the study, patients will be given a FACT-Cog questionnaire and undergo MRI imaging. The study invention will be conducted for six months where patients will use the ARMCan app for 15 minutes daily. They will be followed for one year post-study intervention with FACT-Cog questionnaires given directly after the cessation of the study intervention and at months six and 12 of follow up. An additional MRI will be taken at month 12 of follow up. Results: FACT-Cog and MRI data will be used to analyze the results of active versus receptive music therapy on chemotherapy-related cognition dysfunction. Conclusions: We are currently accruing patients to beta test this interactive application, which may promote executive function recovery in breast cancer patients with chemobrain and advance clinical care in breast cancer survivorship.
National cancer centers addressing climate change: An overview and analysis of organizations' sustainability plans.
Authors: Maniar Ashray , Lichter Katie , Husain Marium , Kishan Raina , Hantel Andrew
Published: June 2022

e13623

Background: Climate change is one of the largest threats to human health and greenhouse gas (GHG) emissions are a substantial component of climate change. In the U.S., the healthcare industry accounts for an estimated 8.5% of GHG emissions, equating to the loss of 470,000 disability-adjusted life-years annually. Cancer care encapsulates a significant portion of hospital resources and climate change has disproportionate effects on cancer patients. Therefore, it is imperative and urgent that cancer centers actively engage in reducing healthcare related GHG emissions. In this systematic analysis and comprehensive review, we reviewed publicly accessible sustainability plans of National Cancer Institute (NCI)-designated Cancer Centers and their affiliated organizations to understand the involvement Cancer Centers have in their organization's sustainability efforts. Methods: We reviewed 64 NCI designated Cancer Centers, using the first 20 results of a Google search with terms: “Hospital X AND (climate action plan OR climate change OR sustainability plan OR carbon neutral)” and hospital homepages to identify publicly accessible sustainability plans for each organization. We reviewed the plans, performed a Google search/Cancer Center homepage search and messaged sustainability plan developers to identify involvement of the hospital and Cancer Center. We identified which hospitals assigned sustainability personnel. We performed a student’s t-test to assess for a correlation between incidence of lung cancer in a state and presence of a sustainability plan for that state’s Cancer Center. Data was collected by one reviewer, independently validated by a separate reviewer and differences were resolved by a joint data review. Results: Amongst the 65 Cancer Centers and organizations reviewed, 55 (36 university, 12 hospital, 7 joint) had publicly available sustainability plans. Of which, 31% (11/36) of university plans explicitly mentioned an affiliated hospital as part of the sustainability plan. Two Cancer Centers (3%) had independent sustainability plans and 7 (11%) centers mentioned sustainability on their homepage. 77% (23/30) of hospitals with sustainability plans identified sustainability personnel. We did not find an association between the existence of Cancer Center sustainability plan and that state’s lung cancer incidence rates (p = 0.932). Conclusions: In this review and analysis of NCI-designated Cancer Center sustainability plans, we found that while most centers’ affiliated organizations have publicly accessible sustainability plans, the majority (86%) of centers do not independently report on their sustainability efforts. These findings highlight a pressing need to increase engagement between Cancer Centers and their organizations regarding sustainability plans, and a need for greater transparency in publicizing sustainability plans.
Practice consolidation among U.S. medical oncologists over time.
Authors: Milligan Michael , Erfani Parsa , Orav E. John , Brooks Gabriel A. , Lam Miranda
Published: June 2022

e13627

Background: Physician practices across the U.S. are increasingly merging with hospitals and other practices. The extent of such “practice consolidation” varies by specialty and across geography but has not been well characterized within medical oncology. Methods: Utilizing Medicare data, we identified all medical oncologists (MO) who billed for Medicare services each year between 2015 and January 2022. We associated each physician to one or more unique practices via organizational Taxpayer Identification Numbers (TIN), and classified practices by the number of medical oncologists—including solo (1 MO), small (2-10 MOs), medium (11-24 MOs), and large (25+ MOs) practices. We defined the extent of regional healthcare markets according to Hospital Referral Regions (HRRs), and calculated levels of practice consolidation using the Herfindahl-Hirschman Index (HHI). The HHI is a commonly used measure of consolidation, calculated by summing the square of each practice’s market share. HHI values range from 0 to 1 with higher numbers indicating greater consolidation and less competition among practices. Finally, we generated a multivariable linear regression model to determine which regional market factors were associated with changes in levels of medical oncology practice consolidation over time. Results: Between 2015 and 2022, the number of practices with MOs in the U.S. declined 18.0% from 2,774 to 2,276, while the number of practicing MOs increased 14.5% from 11,727 to 13,433. The median medical oncology practice HHI increased from 0.3204 to 0.3480. Over time the proportion of solo practices fell (48.4% in 2015, 43.9% in 2022) while the proportion of medium and large practices increased (medium: 5.7% to 8.4%; large: 2.7% to 4.5%). By 2022, large practices had grown to employ a significantly larger proportion of all medical oncologists (33.6% to 43.7%, p < 0.001). Between 2015 and 2022, the proportion of practices solely comprised of MOs (as opposed to multispecialty practices) decreased from 40.0% to 28.2%. On multivariable analysis, HRRs with higher levels of hospital consolidation (p < 0.001), greater numbers of hospital beds per 1,000 persons (p = 0.02), and a lesser degree of baseline medical oncology practice consolidation in 2015 (p < 0.001) experienced more consolidation during the study period. Conclusions: Medical oncologists across the U.S. are increasingly working in larger practices. By 2022, more than 40% of all practicing MOs were employed at the largest 5% of practices. Consolidation of medical oncology practices occurred more readily in regions with higher levels of hospital consolidation and a greater supply of hospital beds, suggesting that integration into hospital systems may be a leading source of consolidation. Further study is required to determine the impact of practice consolidation on the cost, quality, and accessibility of cancer care.
The impact of the multidisciplinary team (MDT) in the management of colorectal cancer (CRC).
Authors: Anghelone Annunziato , Bensi Maria , Barbaro Brunella , Calegari Maria Alessandra , Cina Caterina , Menghi Roberta , Lorenzon Laura , Pozzo Carmelo , Basso Michele , Schietroma Francesco , Valente Giustina , Lococo Filippo , Ardito Francesco , Cellini Francesco , Caira Giulia , Trovato Giovanni , D'Ugo Domenico , Giuliante Felice , Tortora Giampaolo , Salvatore Lisa
Published: June 2022

e13641

Background: The management of CRC is complex, particularly in metastatic disease, where it is crucial the definition of disease burden, the assessment of radiological response and the identification of the right timing for potential radical surgery or loco-regional treatments. A correct CRC evaluation and the subsequent choice of the most appropriate treatment strategy, need, therefore, a MDT involving surgeons, oncologists, radiologists, radiation oncologists, endoscopists, gastroenterologists and pathologists. Based on such considerations, we investigated the impact of the MDT meeting in the management of CRC at our Institution. Methods: We retrospectively evaluated all the cases discussed at our MDT meeting between September 2019 and September 2021. We collected data, both pre- and post-MDT meeting, regarding radiology evaluation (disease control vs progression), surgical assessment (yes vs no) and radiotherapy evaluation (yes vs no). Primary endpoint was the overall rate of discrepancy in evaluation between pre- and post-MDT meeting. Results: Between September 2019 and September 2021, 696 cases were presented at our MDT meeting. The median age was 65 years (24-86), 391 (56%) patients were male and 553 (79%) patients had metastatic disease at diagnosis. After MDT meeting, a total of 214 decisions were modified, for an overall discrepancy rate of 31%. In particular, among 377 cases discussed for radiology evaluation, 110 decisions (29%) were modified after a central imaging review: 80 cases initially evaluated as progressed disease before MDT meeting were defined stable after MDT meeting, for a discrepancy rate of 73%. Regarding the 246 cases discussed for surgical assessment on primary tumor and/or metastatic sites, treatment strategy changed in 86 cases (35%). More specifically, 16 cases (19%), evaluated unresectable before MDT meeting, were then considered resectable after MDT meeting. Finally, among the 71 cases discussed for radiotherapy evaluation, treatment strategy changed in 18 cases (25%). Conclusions: Our analysis demonstrates a significant rate of discrepancy in radiology and/or surgical evaluation between pre- and post-MDT meeting. Our results show that a MDT allows a considerable modification in CRC management, maximizing the treatment strategy, in particular avoiding unnecessary changes in therapy and allowing surgery where possible.
Clinicians’ perspective on use of immune checkpoint inhibitors and related biomarkers for solid tumors.
Authors: Moser Kaitlynn , Lindpaintner Klaus , Soto Michelle , Geba Daniela , Allen Paul
Published: June 2022

e13643

Background: Immune checkpoint inhibitors (ICIs) are a valuable treatment option for patients with malignant tumors, but only selected patients respond to ICIs. Available biomarkers are of limited use in guiding ICI therapy. We sought to examine clinicians’ perspective on the use of ICIs and biomarkers for treatment of malignant tumors and to identify unmet needs related to their use. Methods: We conducted in-depth telephone interviews of eight oncologists, and 100 oncologists completed online surveys. Results: Oncologists have a positive attitude toward use of ICIs, and 98% of them prescribe them in all approved indications. Clinicians report that only about half of the patients with solid tumors responded to treatment, overestimating the response rate to ICIs across most types of tumors they treat, compared with data in the literature. They ranked the lack of reliability of biomarkers to guide treatment (rating of 4.4 out of 7) as the top challenge with use of ICIs, followed by lack of overall efficacy and toxicity or occurrence of immune-related adverse events. The biomarkers most often used by survey participants were: a comprehensive panel including driver mutations and tumor mutational burden (69% of respondents), programmed cell death ligand-1 (PD-L1) expression (62%), and microsatellite instability (MSI) (56%). Oncologists indicated that they ordered biomarkers for each type of cancer according to their perceived usefulness of each biomarker in predicting the outcomes for ICI therapy, being more likely to use those perceived as useful or very useful. Conclusions: Clinicians indicate that more reliable therapy-response prediction biomarkers would have a great impact on treatment decisions for patients with solid tumors, reducing unnecessary treatments, side effects, and health care expenditures.
Assessment of telehealth experience among a head and neck oncology population.
Authors: Hung Kin Wai (Tony) , Cracchiolo Jennifer R. , Kim Soo Y , Gillespie Erin F. , Pfister David G.
Published: June 2022

e13650

Background: Studies suggest that oncology patients are satisfied and sometimes prefer telehealth over an in-person visit; however, data are scarce on when patients find telehealth helpful. Such information would be key in understanding how telehealth can be optimally integrated into cancer care delivery. This study aims to identify factors that influence patient experience of telehealth among a multidisciplinary head and neck oncology population. Methods: From Mar 2020 to Dec 2020, we surveyed head and neck oncology patients at a comprehensive cancer center and 6 satellite sites in New York and New Jersey. We assessed patient experience of telehealth versus in-person visit (primary outcome) and their satisfaction with telehealth (secondary outcome). We conducted multivariate regression to analyze covariates that may influence their experience and satisfaction. Covariates included patient factors (age, gender, race, marital status, primary language, home state, home distance from center, current location at home or clinic), clinical factors (diagnosis, performance status, receiving chemotherapy or radiation), physician factors (profession, current location at main or regional campus), visit factors (type, length, billing level, month, first telehealth visit or not), and a technological factor (device type). Results: Among 1,071 completed surveys (response rate 24.0%), 551 first-unique surveys were analyzed. Surveyed patients were predominantly 60 years or older (64.1%), white (88.3%), married (73.8%), and lived within 50 miles from our cancer center (76.1%). Majority had diagnoses of head and neck cancers (65.7%), followed by thyroid cancers (23.8%), and skin cancers (10.5%). While most patients would recommend telehealth (82.4%), only half reported telehealth the same or better compared to in-person visits (55.7%), whereas the other half reported not as good or unsure (44.3%). In multivariate analyses, patients who found telehealth the same or better than in-person visits were more likely to have thyroid cancers (adjusted odds ratios [aOR]: 2.18, CI 95% 1.44 - 3.36) and have visits from July to December (aOR 1.61, CI 95% 1.14 - 2.27). Satisfaction with telehealth was higher among patients with thyroid cancers (aOR: 2.58, CI 95% 1.20 - 6.41), on visits when patients were at home (aOR 3.48, CI 95% 1.37 - 8.42) and when physicians were on campus (aOR 1.73, CI 95% 1.00 - 2.99). Conclusions: Patient experience with telehealth is diverse among the head and neck oncology population; while one-half found telehealth the same or better compared to in-person visits, the other half found it not as good or unsure. More favorable telehealth experience among patient subgroups highlights the multidisciplinary nature of head and neck oncology and improved acceptance of telehealth over time. Future research to optimize patient experience is needed to ensure successful integration of telehealth in head and neck oncology practices.
Anlotinib in combination with dose-intense temozolomide for the recurrent or progressive glioblastoma after STUPP regimen.
Authors: Yang Qun-ying , Guo Cheng-cheng , Mou Yong-gao
Published: June 2022

e14014

Background: Nearly all patients (pts) with glioblastoma (GBM) will suffered relapse or disease progression after resection and adjuvant radiotherapy and temozolomide (TMZ). Anlotinib is a new multikinase inhibitors (MKI) blocking angiogenesis and tumor cell proliferation simultaneously and a prospective phase II study was performed to explore the potency of the combination anlotinib and TMZ for pts with relapse or progression GBM. Here, we reports the preliminary results of this study. Methods: This is a prospective, single-arm, open label, phase II study (NCT04547855). Eligible pts were diagnosed with histologically confirmed glioblastoma and experienced relapse or progression for the first time from surgery (including biopsy, partial resection and total resection) and radiotherapy-TMZ therapy (STUPP regimen). Other criteria included 18 to 75 years age, Karnofsky performance status (KPS) ≥ 60% and adequate organ function. The primary endpoint was progression free survival at 6 months (6m-PFS). All pts received orally TMZ (150 mg/m2) from D1-D7 every 2 weeks and anlotinib (12mg, QD) from D1-D14 every 3 weeks until disease progression or unacceptable toxicities. Results: From July 2020 to November 2021, 25 pts were enrolled. The median age was 49 (rang: 23, 62) and the median KPS was 80 (range: 60, 100). Most pts had poor prognostic factors that 17 pts (70.8%) had unmethylated MGMT promoter and 22 pts (91.6%) were IDH wild-type, which 24 pts detected IDH and MGMT status. At the data cutoff date on January 2022, the 6m-PFS was 25.2% and the median PFS was 4.2 months (95% CI, 3.4-5.0m). The median OS reached 9.1 months (95% CI, 8.1-10.2). Tumor response was assessed for all pts. 7 pts achieved partial response and the objective response rate was 28%. 10 pts had stable disease and the disease control rate was 68%. The most common grade 3 or worse adverse events (AEs) was lympyhopenia (48.0%), which may be caused by TMZ. No death was attributed to AEs. Conclusions: Combination of anlotinib and dose-intense temozolomide was tolerable in the treatment of recurrent or progressive glioblastoma. Preliminary results indicated that the efficacy was promising for those miserable pts with worse prognosis factors. Further investigation was ongoing. Clinical trial information: NCT04547855.
Detection of high-grade glioma clusters: Spatial case-control study using EMR data from 2010-2021.
Authors: Aulakh Sonikpreet , Kimble Wesley , Hendricks Brian
Published: June 2022

e14016

Background: High-grade gliomas (HGGs), like Glioblastomas (GBMs), are the most common malignant intracranial tumors with dismal prognosis. Rural areas have higher HGG related mortality and lesser research advancements. The objective of this study was to identify zip codes with disproportionate risk of HGGs compared to other brain malignancies. Methods: Patients’ electronic health data for this case-control study was extracted from West Virginia University Hospital Systems, 2010-2021. HGG cases were defined using diagnoses codes ICD10-C71 and ICD9-191 (excluding low grade gliomas). The control group was defined by using diagnoses codes ICD10-D32, C79.3, C71 (excluding HGG cases) and ICD9-225.2, 225.4, 198.3, 191 (excluding HGG cases). Controls were exact matched four controls to every case based upon patient five-year age categories and gender. Clustering was assessed globally through difference in Ripley’s-K between cases and controls; and locally using scan statistics. Results: The locations of HGGs and other brain tumors were clustered in the northern and northeastern regions of WV. Global cluster analyses detected statistically significant dispersion of HGG cases compared to our control group. Local cluster analysis identified multi-zip code cluster of HGG patients in northeastern WV between 2010-2021. The average relative risk of HGG compared to other brain malignancies was 1.25, indicating a 25% increase in risk of HGGs compared to other brain cancers within this region. While the local cluster was not statistically significant, the zip code level estimates of relative risk within the cluster ranged from 0.00 to 5.01. This indicated that certain zip codes within the cluster had five times the risk of HGGs compared to non-HGG brain malignancies relative to zip codes outside of the cluster. Conclusions: Findings indicate community level disparities in risk of HGGs relative to other brain malignancies. Additionally, results suggest that HGG cases are seen across the state at a more dispersed pattern than for non-HGG related brain tumors. These overall spatial trends could potentially be attributable to differences in clinical practice, access to care, or social determinants of health throughout WV. Spatial multivariable modeling techniques are needed to identify the specific neighborhood level factors associated with disproportionate patterns of risk identified for WV HGG patients.
A phase II study of anlotinib combined with temozolomide in the treatment of patients with recurrent glioblastoma.
Authors: Xu Qingsheng , Chen Qun , Zheng Xiujue , Cai Jinquan , Zhan Renya
Published: June 2022

e14021

Background: Glioblastoma (GBM) is a highly vascularized tumor and there are few treatment options after disease recurrence. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with temozolomide in the treatment of these patients. Methods: This is an open-label, single-arm, phase II trial (ChiCTR2000028957). Patients with histologically confirmed GBM with definite progression after surgery followed by radiotherapy and temozolomide chemotherapy were eligible for inclusion. Additional inclusion criteria were 1) 18-70 years old, 2) KPS≥60, 3) disease progression on MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria at least 12 weeks (wks) after completion of radiotherapy，4) antiangiogenic therapy naïve. All patients received temozolomide (150-200mg/m2, orally, QD, d1-5/4wks) and anlotinib (10mg, orally, QD, d1-14/3wks) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR, defined as partial and complete responses according to RANO criteria). Safety assessment was done in patients who received at least one dose of study agent. Results: Twenty-one patients (9 males and 12 females) were enrolled between May 2020 and July 2021, and the median age is 55 (range 27-68) years old. Molecular pathological types included MGMT promoter methylated (n = 5), IDH mutation (n = 5), 1p/19q codeletion (n = 8), and TERT promoter mutation (n = 12). Analyses included data collected through December 15, 2021. Tumor response occurred in 17 patients, of which 9 patients had a complete response, and ORR was 81.0% (17/21). There were also 3 patients achieved stable disease and the disease control rate was 95.2% (20/21). Median progression-free survival (PFS) was 13.2 months [95%CI 3.90-22.52], and the PFS at 6 months was 60.0%. The incidence of adverse events of grade 3 was 28.6%, with a higher incidence of elevated AST (25.0%) and ALT (20.0%), hypertension (16.7%), leukopenia (15.4%). No grade 4 or treatment related death occurred in this study through the follow-up. Overall, toxicities are mild and manageable. Conclusions: Anlotinib combined with temozolomide is efficacious and well-tolerated in recurrent GBM patients. Clinical trial information: ChiCTR2000028957.