bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world survival outcomes associated with use of pertuzumab and trastuzumab emtansine (T-DM1) for HER2-positive (HER2+) metastatic breast cancer (MBC) in Brazilian private healthcare setting.
Authors: Dienstmann Rodrigo , Cruz Heloisa , Coelho Gonçalves Aline , Andrade Diocesio Alves Pinto de , Liedke Pedro Emanuel Rubini , Costa Rafael Brant , Dantas Loures da Costa Mario Alberto , Boukai Alexandre , Paes Flavia Rocha , Landeiro Luciana G. , Gimenes Daniel Luiz , Magalhaes Maria Cristina Figueroa , Resende Cristiano Augusto Andrade de , Reinert Tomas , Aguiar Junior Pedro N. , Paes Rafael , Costa e Silva Matheus , Ferrari Bruno Lemos , Mano Max S.
Published: June 2022

e13022

Background: Breast cancer is a leading death cause of women in Brazil. There are increased concerns with limited access to innovative therapies and the effectiveness of these agents outside clinical trials. This study aims to assess practice patterns and real-world outcomes of patients with HER2+ metastatic breast cancer (MBC) treated in the largest network of community oncology practices of Brazil after the introduction of pertuzumab and T-DM1 in routine care. Methods: De-identified electronic medical records from Oncoclínicas Group were aggregated in a cloud-based central database that allows technology-based abstraction, whereby trained data curators qualify the information using mCODE standards. We included data from all patients with a confirmed diagnosis of HER2+ MBC treated from 2014 to 2021. The primary objective was median overall survival (OS) from diagnosis of metastatic disease and other endpoints included adoption of pertuzumab-based regimen and T-DM1 in the palliative setting and their median Time to Treatment Discontinuation (TTD) in a real-world scenario. Results: Out of 21,559 patients with BC in our database, 6,215 had HER2+ disease and 1,250 had MBC treated with at least one palliative anti-HER2 therapy. Median age at diagnosis was 56 years, 29% had de novo metastatic disease, 81% received 2nd line therapy and 47% a 3rd line or beyond. With a median follow-up of 2 years, median OS was 49 months (CI95% 44-59). We found a ten-fold increase in the proportion of patients receiving pertuzumab or T-DM1 in the last two years when compared to 2014-2015. Overall, 62% received a pertuzumab-based regimen, mostly in the 1st line (76%), with median TTD of 9.9 months (CI95% 9-13). T-DM1 was accessible to 22% of the patients, mostly in 2nd (28%) or 3rd line and beyond (50%), with median TTD of 10.2 months (CI95% 9-13). Conclusions: In the largest Brazilian real-world study of patients with HER2+ MBC treated in the private health system, we found similar outcomes as those reported in North-American and European cohorts, both in terms of OS and TTD with standard-of-care therapies. Adoption of pertuzumab and T-DM1 was fast, but there are still gaps in access and the need to optimize clinical positioning of new anti-HER2 therapies recently approved for clinical use.
Maintenance endocrine therapy prolonged progression-free survival of first-line chemotherapy with trastuzumab in advanced HR-positive, HER2-positive breast cancer patients.
Authors: Shen Xia-Bo , Wu Jia-Yi , Chen Ke-Yu , Fang Zi-Ru , Li Guang-Liang , Zou Wei-Bin , Wang Xiaojia , Shao Xi-Ying
Published: June 2022

e13023

Background: Human epidermal growth factor receptor-2 (HER2) positive breast cancer is a growing concern due to the boom in anti-HER2 therapy. Trastuzumab as the most classic anti-HER2 therapy drug, combined with chemotherapy has become the standard first-line treatment for advanced HER2-positive (HER2+) patients. Although some real-world studies of trastuzumab have been reported, less is known about the role of hormone receptors (HR) in first-line combined therapy. For maintenance therapy after chemotherapy combined with anti-HER2 therapy, the guidance given by clinical trials is the maintenance of targeted therapy. However, for those with HER2+/HR-positive (HR+) breast cancer, whether adding endocrine maintenance therapy can benefit progression-free survival (PFS) in addition to anti-HER2 therapy still needs more research. Thus, the purpose of this study was to retrospectively analyze real-world data, determine the factors that influence the trastuzumab-based therapy in advanced HER2-positive breast cancer patients. Methods: We retrospectively collected the treatment information of advanced breast cancer patients underwent first-line chemotherapy with trastuzumab from 2012 to 2021 in Zhejiang Cancer Hospital. Kaplan–Meier analysis and Cox regression methods were used to calculate and compare the PFS. Results: The study finally enrolled 285 patients meeting the requirement, including 150 HER2+/HR-negative (HR-) and 135 HER2+/HR+ (triple-positive) patients. The median chemotherapy treatment cycles and trastuzumab cycles were 7 (6-8) and 12 (7-17) cycles, respectively. For triple-positive breast cancer, maintenance endocrine therapy was aslo given concurrently with trastusumab in 75 patients after chemotherapy and trastusumab. Overally, the median PFS of first-line treatment was 11.73 (10.16-13.30) months, which was consistent with literature reports. Multivariate analysis revealed that HR positive [hazard ratio, 0.69; 95% confidence interval (CI), 0.52–0.92; P= 0.010], and non-brain metastasis (hazard ratio, 0.54; 95% CI, 0.29–0.99; P= 0.048) were independent prognostic factors. Further Kaplan–Meier analysis demonstrated triple-positive patients with maintenance endocrine therapy significantly had longer PFS than triple-positive patients without maintenance endocrine therapy and HER2+/HR- patients (21.33m vs. 10.13m vs. 9.53m, respectively, P < 0.001). Conclusions: HR-positive was an independent prognostic factor for HER2-positive advanced breast cancer patients receiving first-line chemotherapy with trastuzumab. And endocrine therapy combined trastuzumab as Maintenance after chemotherapy prolonged PFS in HR-positive subgroup patients.
Efficacy and safety of palbociclib in treatment of HR-positive advanced breast cancer patients: A single center real-world experience.
Authors: Vaid Ashok K. , Sharma Devender , Wadhwa Jyoti , Sharma Nagender , Mishra Saurabh , Gautam Dheeraj , Sen Ashok , Raju Anisha , Yadav Lavina , Verma Girdhar
Published: June 2022

e13035

Background: With an estimated 2.3 million new cases (11.7% of all cases), female breast cancer is the leading cause of cancer globally as of 2020. Metastatic or advanced breast cancer is an incurable disease with a 5-year overall survival rate of 28.1%. Palbociclib, a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor, is approved to treat HR+/HER2- metastatic breast cancer (MBC). The present single-arm study evaluates the real world experience of efficacy and safety of Palbociclib-Letrozole for the treatment of HR+/HER2- MBC in the Indian population. Methods: MBC patients with or without prior chemotherapy and hormone therapy were treated with Palbociclib 125 mg once daily (3/1 schedule) plus Letrozole 2.5 mg once daily. The efficacy was recorded as objective response or disease control rate based on the response as per the RECIST criteria. The study also reports the incidence and severity of adverse events during the treatment duration. The tolerability was assessed per Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA) v.21.0. Results: A total of 102 patients were treated from 2017 to 2020 at the tertiary cancer center. The efficacy response is captured as per the investigator's assessment of the disease response. The response is as captured for 100/102 patients (two patients lost to follow-up) and are represented in Table. About 17% (23/100) patients achieved an objective response, while 54% (57/100) showed disease control. The tolerability was assessed as treatment-related side-effects (adverse events (AEs) and severe adverse events (SAEs)) as reported by the treating oncologist. Overall, 61 adverse events were observed in 40/102 (39.22%). The most-reported AE, neutropenia, was reported in 13 patients, followed by chest pain and breathlessness. Conclusions: In the present study, Palbociclib + Letrozole reported good clinical response at the end of treatment duration with a manageable tolerability profile in the Indian population.
Prophylactic use of metformin in patients on alpelisib treatment.
Authors: Filonenko Daria , Zhukova Lyudmila
Published: June 2022

e13040

Background: Alpelisib-induced hyperglycemia (HG) is the most common adverse event leading to interruption, reduction or withdrawal of the treatment. HG is an on-target effect that depends on the baseline metabolic status of the patient. In SOLAR-1 90,6% patients with high-risk at baseline HG G3/G4 was reported. Prophylactic use of metformin may prevent HG in patients at risk. Methods: HR+ HER2-negative advanced breast cancer patients were stratified to low-, moderate- or high-risk groups of HG based on the algorithm published in [1] before starting alpelisib 300 mg + fulvestrant (Alp + Fulv). Moderate- and high-risk patients used prophylactic metformin at 500-1000 mg or 2000 mg BID with breakfast and dinner (Table). Metformin was started at least one-week prior Alp administration. Fasting plasma glucose (FPG) was monitored qw and bw in low- and moderate-risk patients, and daily with home glucometer in addition to bw FPG for high-risk patients. The primary endpoint of retrospective analysis was to assess the incidence of HG G3/G4 in different risk groups based on CTCAE V4.03 guidelines. Results: A cohort of 18 patients (median lines of previous treatment in advanced disease was five, all patients has received CDK4/6 inhibitors) treated with Alp+Fulv in the Loginov Moscow Clinical Scientific Centerin 2020-2021 included 7 low-, 3 moderate- and 8 high-risk patients. Any grade HG was reported in 13 out of 18 pts; no cases of HG G2 or G4 were detected. HG G3 was reported in 5 out of 18 patients including in 2 out of 3 moderate-risk patients, and in 3 out of 8 high-risk patients. Anti-HG drugs used included metformin (6/18); empagliflozin (4/18), and linagliptin (1/18); 1 patient required Alp dose reduction to 250 mg due to HG G3; none discontinued Alp due to AEs. Other AEs included rash (7/18; no grade 4; grade 3 in 4/18), and blood creatinine increase (8/18 – all grade 1-2).The median PFS on treatment with Alp+Fulv was 7 months. Conclusions: Prophylactic use of metformin in patients with high risk of hyperglycemia could markedly reduce frequency and severity of hyperglycemia on alpelisib.[Table: see text]
Eribulin combined with anlotinib for patients with HER2-negative metastatic breast cancer: A single-arm, multicenter, phase II study.
Authors: Yin Yongmei , Wu Xinyu , Hua Yijia , Sun Chunxiao , Liang Yan , Yang Fan , Huang Xiang , Li Wei
Published: June 2022

e13051

Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor with a distinct mode of action which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of combined treatment with eribulin and anlotinib in patients with HER2-negative metastatic breast cancer (NCT04624711). Methods: This open-label, single-arm, phase II study enrolled females with HER2-neagtive breast cancer who underwent ≥1 line chemotherapy, including anthracyclines and taxanes, for metastatic breast cancer. Patients with hormone receptor positive breast cancer have underwent ≥1 line endocrine therapy. All patients were treated with Eribulin mesylate (1.4mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to February 2022, 25 patients were enrolled in this study. Median follow-up was 3.45 months (95% CI 3.16-5.06). Median PFS was 4.6 months (95% CI 3.55-5.65). Of all the patients whose efficacy could be evaluated (21/25), no patient achieved complete response (CR); 9 (40.91%) and 10 (45.45%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 40.91% and DCR was 86.36%. OS has not reached. The major treatment-related adverse events (incidence≥10%) were neutropenia(48.00%), anemia(37.93%), platelet count decreased (34.48%), fatigue (31.03%), hypoalbuminemia (20.69%), constipation (13.79%), elevated lactate dehydrogenase(13.79%), lymphocyte count decreased (10.34%) and hypertriglyceridemia (10.34%). The most common grade 3/4 adverse events were neutropenia (20.00%). 16.00% (4/25) of patients had dose reductions. Conclusions: The combination of eribulin and anlotinib showed a better treatment response and tolerable toxicity in HER2-negative metastatic breast cancer patients. Further studies enrolling more patients are still needed. Clinical trial information: NCT04624711.
Survival outcomes in patients with metastatic breast cancer treated with eribulin: A real-world evidence study from India.
Authors: Vaid Ashok K. , Wadhwa Jyoti , Sharma Nagender , Sharma Devender , Sen Ashok , Gautam Dheeraj
Published: June 2022

e13053

Background: Eribulin is a novel synthetic analogue of halichondrin B, which acts as a microtubule inhibitor by interacting with the microtubules and inhibits the G2-M growth phase. Eribulin was approved for metastatic breast cancer (MBC) based on landmark EMBRACE (phase-3) trial, although only a small number of Asian subgroups of the population were included, and data in the Indian subset of patients is limited. Therefore, in this real-world study we retrospectively assessed the clinical outcomes of eribulin in Indian women with metastatic breast cancer (heavily pre-treated). Methods: Adult MBC patients who had advanced following at least two chemotherapy lines, including anthracyclines and taxanes, in either an adjuvant or metastatic setting and were treated with eribulin over several lines were retrospectively analyzed. Records pertaining to socio-demographics, clinical, pathology, imaging, and therapy were reviewed. The overall survival (OS), progression-free survival (PFS), and tumor response were calculated. Results: A total of 80 patients were included. The median age of patients was 54.5 years (range: 27-82). Eribulin was majorly used as a second-line and third-line chemotherapy agent in 28 (35 percent) and 24 (30 percent) of MBC patients, respectively. In 57 evaluable patients, the best objective response rate (ORR) was 43.85 percent, while the clinical benefit rate was 59.65 percent with eribulin therapy. The median OS and PFS were 17.29 (95 percent CI: 14.31-20.27) and 11.76 (95 percent CI: 9.5-14.02) months, respectively. There was positive correlation between the number of cycles and the outcomes of survival, with patients getting more than 6 cycles having superior OS and PFS. On subgroup analysis, patients with liver metastasis had significantly (p<0.001) lower mean OS (9.42 months) and PFS (3.69 months) than other sites. Conclusions: This real-world retrospective study supports and confirms the efficacy of eribulin in Indian patients with MBC (heavily pre-treated). It should be considered in the strategy of several chemotherapy lines in MBC.
Apatinib plus etoposide as second-or higher-line treatment in recurrent or metastatic triple-negative breast cancer: A single-arm, open label, prospective, phase II clinical trial.
Authors: Cao Mengru , Lu Hailing , Yan Shi , Pang Hui , Sun Lichun , Li Chunhong , Chen Xuesong , Liu Wei , Hu Jing , Huang Jian , Xing Ying , Chen Yingqi , He Ting , Zhao Danni , Sun Yuanyuan , Zhao Lin , Liu Xiaomeng , Zhang Ningzhi , Cai Li
Published: June 2022

e13069

Background: Due to the lack of targeted therapies, the standard of care for advanced triple-negative breast cancer (TNBC) was still chemotherapy, yet its effectiveness remains unsatisfied. Therefore, an urgent need exists to find a novel treatment option for patients with TNBC. The effect and safety profile of apatinib and etoposide have been demonstrated in several clinical trials for the treatment of late-stage TNBC respectively. In the present study, we aimed to investigate the potential effect of combination therapy of apatinib plus etoposide in recurrent or metastatic TNBC. Methods: Patients with late-stage TNBC who failed at least one line of chemotherapy were recruited in our study. Eligible patients were treated with in a 3-week cycle until disease progression or unacceptable toxicity for up to a maximum of 6 cycles. Apatinib could be declined to 250mg according to patients’ condition. Patients who completed their treatment were followed every 8 weeks and their disease progress was assessed scans according to RECIST 1.1. The primary endpoint was progress-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Safety was also evaluated. Results: From August 2018 to September 2021 a total of 40 patients were enrolled in this study. Their median age was 56-year old (range, 27-76) and had received a median of 3 (range, 2-6) previous lines chemotherapy. Until January 2022, among all eligible patients, 30 PFS events were observed. The median PFS was 6 months (95% CI, 3.77̃8.23) and the median OS was 24.53 months (95% CI, 10.23-38.83). Meanwhile, 4 patients achieved partial response, 21 patients achieved stable disease, the ORR was 10% and the DCR was 62.5% In addition, the most common adverse events were hypertension (65%), nausea (47.5%), vomiting (42.5%), and hand–foot syndrome (32.5%). The most common grade ≥ 3 adverse events were hypertension (5%) and proteinuria (5%). Conclusions: The results of the study exhibited a promising clinical effect of the combination therapy of apatinib plus etoposide and acceptable toxicity in recurrent or metastatic TNBC as second-or higher-line treatment. And more results will be updated with the progress of this clinical trial. Clinical trial information: ChiCTR1800018497.
Results of the safety run-in of gedatolisib plus talazoparib in advanced triple negative or BRCA 1/2 positive HER2 negative breast cancer.
Authors: Phadke Sneha Deepak , Yu Menggang , Miller Kathy , Shah Ami N. , Danciu Oana Cristina , Wisinski Kari Braun
Published: June 2022

e13075

Background: Metastatic triple negative breast cancer (TNBC) is a disease subtype with a poor prognosis, though advancements have been made in the use of targeted therapies, such as poly (ADP-ribose) polymerase inhibitors (PARPi) for those with germline BRCA 1/2 mutations. Up to 2/3 of TNBC tumors have acquired defects in homologous recombination (HR) DNA repair, yet PARPi monotherapy has been ineffective in extending survival in these patients. Phosphoinositide-3-kinase (PI3K)/mTOR pathway alterations are also common, and preclinical data supports that PI3K/mTOR inhibition may disrupt normal function of the HR complex and increase dependency on PARP enzymes for HR DNA repair. Thus, combining a PI3K/mTORi with a PARPi may result in a synergistic anti-neoplastic effect. Methods: The safety run-in portion of this study evaluated the safety and preliminary efficacy of the combination of weekly IV gedatolisib (PI3K/mTORi) and continuous daily talazoparib. Germline BRCA mutations were not required. The safety run-in was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). A 3+3 design was utilized for dose escalation, with starting dose at level 1. Dose levels are as shown in the Table. Eligibility criteria included patients ≥ age 18 who had received 1-3 prior lines of therapy for advanced TNBC or advanced HER2-negative BC with a germline BRCA 1/2 mutation. Those with untreated CNS metastasis were excluded as were those type I diabetes or uncontrolled type II diabetes, due to the risk of hyperglycemia with gedatolisib. Results: A total of 14 female patients were enrolled on to the safety run-in phase of the trial. Median age was 53 (range 30-67). Most patients (79%) were Caucasian, 14% were African American, and 7% unknown. The most common adverse events (AEs) of any grade were fatigue, anemia, nausea, and oral mucositis. Grade 1 hyperglycemia was noted in about 1/3 of the cohort, with 1 grade 3 event. There were 3 patients who experienced grade 4 AEs, thrombocytopenia (2) and lymphopenia (1). There was 1 DLT of grade 3 neutropenia which occurred at dose level 1. The MTD of gedatolisib was 180 mg and MTD of talazoparib was 1 mg. In this preliminary cohort, 3 patients achieved PR and 5 patients achieved SD. Median duration of PR was 13.34 months and median duration of SD was 4.11 months. Of the 3 patients with a BRCA 1 or 2 mutation, 2 had a best response of PR and the other SD. Conclusions: The safety run-in indicated that this combination is safe and well tolerated with mostly grade 1-2 AEs. This combination therapy has moved into the phase II trial, with 2 cohorts. Cohort A includes BRCA-wildtype patients with TNBC and cohort 2 includes those with a BRCA mutation and HER2-negative disease. Clinical trial information: NCT03911973. [Table: see text]
Evaluating anticancer agents on 3D bioprinted organoid tumors (BOT) to reduce cost and accelerate therapeutic discovery.
Authors: Patel Zeelu H. , Charania Areesha A. , Punjani Zeenia , Patel Heli K. , Sewell-Loftin Mary Kathryn , Saleh Mansoor N. , Budhwani Karim I.
Published: June 2022

e13500

Background: Despite recent advances in therapeutics, cancer remains the second leading cause of death worldwide. Next generation cancer models hold the promise of breaking this stranglehold. However, extracting adequate tissue for precision and personalized medicine ex vivo models can be difficult depending on tumor type and tissue site. Mechanisms to expand tissue include patient derived xenografts and patient derived organoids. The former imposes a large time window to establish while the latter is constrained in space by sizescales. Advances in 3D bioprinting have improved the ability to reproduce the three-dimensionality and heterogeneity of the tumor microenvironment. Here we present a novel mechanism to address space and time constrains with 3D bioprinted organoid tumors (BOT) that mimic core needle biopsy tissue to reduce both cost and time to market for novel therapeutics making effective cancer therapy more accessible and equitable. The aim of this study is to produce and use BOT core biopsy tissue in ex vivo precision and personalized medicine applications. Methods: Bioinks prepared with MDA-MB-231 cells, fibrinogen, and thrombin will be deposited layer-by-layer on microporous substrate, in various geometrical configurations, and cured in stages to allow cells and matrix to self-assemble with limited degrees of freedom. Bioprinted organoid tissue will be fully cured to mimic patient biopsy cores, which will then be loaded in ex vivo bioreactors to evaluate sensitivity and resistance of small molecule and biologics. Results: Tissue 3D microarchitecture was validated using high-content fluorescence imaging and custom image processing applications. Diffusion of mock agents, small molecule, and nucleic acid stains was measured 200 mm deep in tissue. Differential activity in spatially distinct regions of intact BOT cores was quantified using advanced image processing modules. Conclusions: Patient derived BOT cores could be used both as a predictive model to screen drugs on an individualized basis and to uncover new therapeutic targets to improve efficacy and reduce toxicity. Due to their ability to replicate the physical and biochemical characteristics of a tumor and its microenvironment, BOT based precision and personalized medicine models can provide more accurate data on drug efficacy and toxicology when compared to in vitro cancer models.
A phase II feasibility study of electronic patient reported outcomes (ePROs) for oral cancer directed therapies (OCDT).
Authors: Doolin Jim W , Haakenstad Ellana , Neville Bridget A. , Lipsitz Stuart R. , Zhang Sunyi , Cleveland Jessica , Hiruy Semegne , Hassett Michael J. , Revette Anna C. , Schrag Deborah , Basch Ethan , McCleary Nadine Jackson
Published: June 2022

e13509

Background: Patients receiving oral cancer directed therapy (OCDT) may be at greater risk of toxicity and non-adherence than those on intravenous treatments. Electronic patient reported outcomes (ePROs) have the potential to mitigate those risks by alerting clinicians to patient status between visits, prompting earlier intervention. Best practices for ePROs implementation are not yet defined. We sought to demonstrate the feasibility of ePROs between visits for patients receiving OCDT both without and with asynchronous nursing triage calls for severe symptoms. Methods: In this Phase II feasibility study, patients were prospectively enrolled into two arms. In the first arm, “passive management” (Arm 1) patients were sent weekly ePROs with 15 symptoms, graded 0 (none) to 3 (severe), through the electronic patient portal (ePP). Responses were available for review by clinicians via the electronic medical record (EMR). In the second arm, “active management” (Arm 2) patients received the same weekly ePROs. If a patient responded with a severe symptom, a nurse would call within one business day to triage the concern. The primary outcome was 30-day feasibility, defined as a patient responding to 50% or more of ePROs sent during this period. Secondary outcomes included feasibility at 60- and 90-days, unplanned healthcare utilization (urgent care, ED visit or hospitalization), and nursing calls. At the time the Arm 2 was enrolling, a language-concordant interface for the EMR and ePP became available. The study was amended to include primarily Spanish speaking patients with a language concordant ePROs survey. Results: 100 patients were enrolled, 50 per arm. 10 patients who primarily spoke Spanish were included in Arm 2; the remaining 90 patients were fluent in English. 96 patients were eligible for evaluation of 30-day feasibility, 92 for 60-day, and 86 for 90-day. The 30-day feasibility by arm was 57% in Arm 1 and 45% in Arm 2 (p = 0.26). The 30-day feasibility in the Spanish language subgroup of the Arm 2 was 56%. Nursing calls in the first 30-days were 101 in Arm 1 and 109 in Arm 2. Multivariable regression for predictors of responding to 50% or more of ePROs in days 0-30 did not identify statistically significant correlates of feasibility. Conclusions: ePROs administered via an ePP were feasible the first 30 days on oral cancer directed treatment. Adding nurse triage calls between visits and a language concordant process for primarily Spanish speaking patients were feasible. Larger studies are needed to determine which factors truly impact use of the program and, most importantly, adherence and quality of life.[Table: see text]
Coordinating a multi-disciplinary team to reduce financial hardship from cancer: A clinic-based financial navigator approach.
Authors: Banegas Matthew P. , Locher Blake W. , Tuzzio Leah , Schneider Jennifer L. , Rivelli Jennifer S. , Henrikson Nora B.
Published: June 2022

e13527

Background: As efforts to reduce financial hardship within oncology settings increase, development of multidisciplinary approaches based on principles of care coordination – effective communication, shared goals, role clarity, handoff – are essential. Cancer Financial Experiences (CAFÉ) is a randomized controlled trial [NCT05018000] of a financial navigation intervention in two regions of Kaiser Permanente. Our objective was to develop workflows for CAFÉ Financial Navigators (CNs) to provide navigation to trial participants by engaging a multidisciplinary team. Methods: Workflows are based on our conceptual framework of unique care pathways to address financial concerns among cancer patients: resolving acute financial needs; planning for out of pocket (OOP) costs; and making cost-informed care decisions. Influenced by user-centered design, we collected multi-stakeholder perspectives through interviews with approximately 39 staff from 15 departments between 2019-2021 including clinicians (e.g. physicians, nurses, social workers), health care staff (e.g. case managers, patient navigators) and operations/business staff (e.g. business operations analysts, financial counselors). Topics included the current state; existing organizational and informal relationships between operations units; and opportunities for improvement relative to current evidence on patient needs for cancer-related financial navigation. Results: We identified several opportunities to create or enhance workflows to provide financial navigation for oncology patients. We also identified organizational barriers that require further work (e.g., providing detailed oncology-specific fee estimates for treatment and OOP costs). Workflows centered the CN as a primary contact for patients to facilitate engagement with services and ensure effective, consistent connections between patients and care delivery and operations units. We developed (1) cost coordination maps outlining the healthcare team member points of contact within departments and sequence of contacts, for addressing each financial pathway and (2) resource directories that detail the unique financial needs, contact information and role for CNs. We maintained these strategic relationships throughout the trial to serve participants and support sustainability. Conclusions: Our multi-stakeholder strategy aligns clinical and healthcare operations workflows to optimize patient experience and outcomes to reduce financial hardship from cancer. Our work suggests research teams can facilitate process improvement within care delivery settings. However, barriers to certain financial navigation processes remain, reflecting future research needs. An oncology-specific financial navigation model supported by multidisciplinary workflows is key to addressing financial hardship from cancer.
Rapidly adapting the clinical research environment at an NCI-designated comprehensive cancer center to the COVID-19 pandemic.
Authors: Lassman Andrew B. , Brogan Frances L. , Shelton Ryan J. , Bentlyewski Edward , Kelsen Moshe A. , Kim Helen , Ruotolo Brenda L. , Rustgi Anil K. , Jurcic Joseph G.
Published: June 2022

e13534

Background: In March 2020, responding to COVID-19, the Columbia University Institutional Review Board (IRB) mandated all research pause in-person activities except studies “offering the potential for direct benefit” to patients. New enrollment was also paused. Columbia University Irving Medical Center concurrently mandated all non-essential employees work remotely, and all feasible patient visits transition to telehealth. The clinical research infrastructure at the Herbert Irving Comprehensive Cancer Center (HICCC) was required to adapt its operations in response. Methods: The HICCC convened an executive committee (EC), consisting of multi-disciplinary leadership, canvassed peer institutions, and engaged the IRB Executive Director (ED), Chief of Infectious Disease, a bioethicist, and others ad hoc. Results: The IRB ED agreed with the EC that all approved interventional therapeutic clinical trials for cancer (n = 554) offered the potential for direct benefit to patients. The EC established an “Emergency Preparedness” standard operating procedure (SOP) with input from the IRB and HICCC Protocol Review & Monitoring and Data & Safety Monitoring Committees. This SOP required assessment of each protocol for risks/benefit, transition to remote processes when possible, and referenced the Code of Federal Regulations allowing changes to a research plan without prospective IRB-approval if “necessary to eliminate apparent immediate hazard”. For new subjects, the EC created a process for enrollment as exceptions to the research pause requiring written justification by the PI that included risk-mitigation strategies and approval by the EC. 116 patients were accrued under this process. All external monitoring and auditing was transitioned to remote. Finally, 25% of research nurses and 10% of coordinators were redeployed to other short-staffed areas of the medical center. After 3 months, the IRB lifted the research pause in tranches, and the EC charged its Disease Based Teams with prioritizing trials to reopen. Accrual nadired at 30% of pre-pandemic levels in June 2020, which fully recovered by March 2021. Conclusions: A centralized research infrastructure working closely with established institutional committees was critical for the unprecedented yet effective and rapid ramp down/up of clinical trials. After 1-year, accrual recovered to pre-pandemic levels, leveraging new processes such as electronic consent, telehealth, and remote work for staff.
Validation study of end-of-life risk prediction model in active chemotherapy patients.
Authors: Hill Melinda S. , Abdo-Matkiwsky May D. , Biran Noa , Chatiwala Jumana , Chen Aileen L. , Childs Julianne Wilkins , Fitzgerald Denis , Graham Deena Mary Atieh , Horkheimer Ian , Levenbach Rachel L. , McLaughlin Joseph Francis , Salwitz Kimberly A. , Smith Frederick P. , Tassan Robert F. , Ejumejowo Akunna J.
Published: June 2022

e13543

Background: In February of 2020, Integra Connect (IC) released a machine learning (ML) risk prediction model called Integra Predict (IP) to predict End-of-Life (EOL) in active chemotherapy patients within the next six months. Pilot Study: Regional Cancer Care Associates (RCCA) physicians rated of likelihood of EOL in the next six months to compare concordance with the IP model predictions. Part 2 (April 2022): Patient date of death updated at the end of the six-month period will undergo post-hoc comparisons. Physician Prediction vs Actual Outcome. Integra Prediction vs Actual Outcome. Methods: A stratified random sample of 265 active chemotherapy patients from 33 RCCA providers was securely emailed via pdf documents or excel sheets to RCCA for each provider. Worksheets contained provider name, patient name, age, cancer type, and the risk of dying in the next six months (Low, Medium, High). The sample included patients from the top 10 cancer types: breast, carcinoma in situ of breast, chronic leukemia, gastro/esophageal, lung, lymphoma, multiple myeloma, pancreatic, prostate, and small intestine/colorectal cancers. The sample was comprised of patients with active chemotherapy in the care of RCCA between July 2021 through September 2021. RCCA emailed the study documentation to each provider and asked providers securely emailed risk assessments to IC. Provider responses for EOL in the next six months were scored categorically - low risk (1), medium risk (2), and high risk (3). Concordance between provider responses and IP risk predictions was determined. E.g., a provider rating of low compared to a risk model rating of high would result in a difference of 1-3 = -2. Results: Forty-two percent (14/33) providers responded to our request to rate patient specific EOL which corresponds to 40% (106/265) patients sampled. Current results have a large standard deviation (0.235) resulting in a large confidence interval (.175, .64) or (18% to 64% concordance). Ninety-five percent of the time concordance will fall in this range. Table: As displayed in Table, provider estimates matched the IP risk score estimates 41.3% of the time. The average concordance between provider risk estimate and IP risk estimate was -0.7, which is almost one risk level lower, range (-1.4, -0.3). Conclusions: Study hypothesized that risk estimates would not be 50% concordant at an alpha of 0.05. 41% are concordant with a large standard deviation of 0.235, which resulted in overlapping confidence intervals. There is no significant difference in the two risk estimates.
Assessment of the quality of multidisciplinary cancer conferences: A prospective observational study.
Authors: Ibekwe Opuruiche , Gaudioso Carmelo , Attwood Kristopher , Whalen Philip , Nwogu Chukwumere E.
Published: June 2022

e13548

Background: Multidisciplinary cancer conferences (MCCs) serve as venues for input from a variety of clinicians in patient management. Research suggests that leveraging technology improves efficiency and effectiveness of MCCs. This study examined the current state of practice in three specialized MCCs before the implementation of a tumor board technology solution. Methods: A single-site prospective observational study was conducted at a comprehensive cancer center. A validated tool was adapted to evaluate the quality of information and discussion at the MCCs. Variables were scored on a 1-5 rating scale (poor to excellent). Audio recordings supplemented the observational data collection. Surveys were also administered to assess participants’ satisfaction with the process and case discussions. Endpoints of interest included time and quality of case preparation, presentation and discussion, and rate of clinical trials consideration. Descriptive statistics were used to summarize the demographic/clinical characteristics of patients and calculate overall scores for the MCC performance. Results: From September 2020 to March 2021, a total of 257 patients were presented at the three MCCs with a median age of 66 years. The distribution of clinical stages (AJCC)1-4 was 30.5%, 11.6%, 17.2% and 7.7%, respectively with 33.0% of the values missing. The overall quality of information presented, and the discussion was deemed average. However, presentation of patient views, case history and MCC chair contribution were considered poor, above average, and excellent, respectively (median scores = 1.0, 3.5 and 5.0). The median time per case presentation and discussion was 9.0 minutes. The median time per case preparation by the radiologist and pathologist was 8.6 and 12.0 minutes, respectively. Two hundred and eighty-three surveys were completed by attending physicians. 77.5% of them agreed that the case discussions were insightful and helped change their minds about the cases discussed and 91.2% were satisfied with the depth of case discussion. The rate of clinical trial consideration was 10.8%. Conclusions: These findings demonstrate various strengths and weaknesses of a conventional approach to MCCs in three disease sites – thoracic, breast and gynecology. A comparison of relevant parameters when a tumor board technology platform is utilized is ongoing. This may address some of the weaknesses identified in our study and extend the benefits of MCCs to more patients.
External validation of machine learning models for prediction of survival in undifferentiated pleomorphic sarcoma.
Authors: Lee Linus , Yi Thomas , Fice Michael , Jones Conor , Klein Evan , Buac Neil , Lopez-Hisijos Nicolas , Colman Matthew W. , Gitelis Steven , Blank Alan T.
Published: June 2022

e13551

Background: Machine learning (ML) algorithms to predict cancer survival have recently been reported for a number of sarcoma subtypes, but none have investigated undifferentiated pleomorphic sarcoma (UPS). ML is a powerful tool that has the potential to better prognosticate UPS. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2015 for cases of histologically confirmed undifferentiated pleomorphic sarcoma (UPS) and malignant fibrous histiocytoma (MFH). Patient, tumor, and treatment characteristics were recorded, and various machine learning (ML) models were built to predict 1-, 3-, and 5-year survival. The best performing ML models were externally validated using an institutional cohort of UPS patients. Results: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.71 to 0.73 at the 5-year time point. Similarly, all ML models performed best at 1-year and worst at 5-year on external validation. The best performing models had c-statistics of 0.81 at the 5-year time point on external validation, demonstrating good performance in survival prediction. Conclusions: Machine learning models perform well for survival prediction in UPS, though this sarcoma subtype may be more difficult to prognosticate than other subtypes. Future studies are needed to further validate the machine learning approach for UPS prognostication. [Table: see text]
A DEIRGs-based immune score model for predicting prognosis and immunotherapy effects in breast cancer.
Authors: Qu Fei , Li Wei , Yin Yongmei
Published: June 2022

e13558

Background: Immune-based strategies have reignited prospect for the treatment of breast cancer(BRCA).Nevertheless, due to the molecular and genetic heterogeneity of tumors, a single biomarker can no longer meet the clinical needs in the highly complex tumor microenvironment(TMB).The main purpose of this study was to explore the immunobiological markers of BRCA prognosis in help to guide patient management and establish personalized risk assessment. Methods: Univariate/multivariable Cox proportional hazards regression and least absolute shrinkage and selection operator (LASSO) Cox analysis was used to establish a DEIRGs-based model in BRCA.GSEA analysis was used to explore biological signaling pathways. The immune infiltration landscape of BRCA was conducted via CIBERSORT algorithms and immunotherapy response was calculated through TIDE algorithm and TMB analysis. Results: In this study, 1178 BRCA samples from The Cancer Genome Atlas (TCGA) were used as the training set, and 140 samples from Gene Expression Omnibus (GEO) database were used as the validation set. Immune-related genes were collected from ImmPort and Innatedb database. A total of 547 differentially expressed immune related genes(DEIRGs) were identified. Enrichment analysis of the DEIRGs revealed that they were involved in the regulation of the P13K-Akt signaling pathway and cytokine–cytokine receptor interaction. To identify the genes most relevant to BRCA, we performed a WGCNA analysis to select the modules with the strongest correlation between the module traits. A signature based on six DEIRGs(CETP, DES, IL33, TXNIP, RNF125, STAT5B) was constructed. These cases were stratified into high- and low-risk groups according to the median risk score. Kaplan–Meier analysis showed that OS in the high-risk group was significantly shorter than that in the low-risk group (P<0.001).The model presented unique characteristics in terms of immune cell infiltration and immune function in TME. The results from the tumor mutation burden(TMB) and tumor immune dysfunction and exclusion(TIDE) analysis revealed that the model could efficiently predict the potential response of immunotherapy. ROC curves were primarily used to assess the predictive power of the prognostic model, with AUC values of 0.736, 0.816 and 0.836 at 10, 15 and 20 years, respectively. More importantly, we researched the relationship between this model and TMB and TIDE score, which confirmed that this signature gave the best prognostic value. Conclusions: We have developed a novel immune score model, which can effectively and efficiently predict the prognosis of BRCA patients as well as the effect of immunotherapy. The high-risk subtype was featured by higher TIDE score and lower TMB. Our findings suggest that immunotherapy may be efficacious for low-risk groups of BRCA patients. The findings can be served as reference for the further research and validation of biomarkers.
Diagnostic efficacy of deep learning-based prediction of origin for patients with cancers of unknown primary.
Authors: Lan Lan , Wang Bin , Sun Haiyan , You Dong , Zhang Yuman , Li Xing , Wang Kai
Published: June 2022

e13560

Background: Despite of routine medical history inquiry, laboratory analysis, histopathological analyses, endoscopy and imaging methods, 3-5% of metastatic cancers are diagnosed with unknown primary (CUP). It poses a considerable challenge as modern therapeutic options for patients with CUP are mainly limited to empirical chemotherapy (paclitaxel, carboplatin, etc.), leading to an overall poor prognosis. In current clinical trials (CUPISCO trial, PACET-CUP trial) targeting CUP for precision therapy, genomic data suggest that only 31% of CUP patients could be matched for at least one targeted or immune agent. The determination of primary tumor origin and genetic mutations could probably provide more therapeutic choices and help to significantly improve the outcome in CUP patients. Methods: To identify the primary lesion of CUP, we built a weighted ensemble model by Automated machine learning, including 13 models ( XGBoost, RandomForestGini, ExtraTreesGini, etc.), using genetic and clinical datasets containing 22,018 patients of 28 tumor types, enrolled between 2016-2021. Our genetic and clinical datasets contained 10 features including age, tumor site, gene alteration, TMB, etc. Among them, 813 sites related to tumor were covered by gene alteration. The 5-fold Cross-Validation method was used to estimate the accuracy of our diagnosis models. Results: The models were evaluated using top-k differential diagnosis accuracy, which measured how frequently the top-k predictions capture any of the primary diagnoses in the reference standard. Our diagnostic model was then performed on 8 CUP patients. All of them were successfully confirmed their diagnosis of primary origin tumor. Among these patients, 2/8 CUP patients have begun relevant systemic therapy based on the confirmed diagnosis: 1 patient with diagnosis of esophageal squamous cell carcinoma receiving the immune combination TP Regimen (Albumin paclitaxel plus cisplatin) and achieved a 9-month PFS; another patient diagnosed as colorectal cancer achieved a 2-month PFS after treatment with Oxaliplatin-based chemotherapy regimen. Preliminary results of our study demonstrated the efficiency of this Artificial Intelligence model for the diagnosis in CUP patients. Conclusions: We developed a diagnostic model on CUP using deep learning based on genomic and clinical data and preliminarily applied in clinic. Genetic characterization of CUP patients contributes to the selection of targeted therapies under unclear diagnosis, whereas our diagnosis model could equally adjust more proper precision treatment for CUP patients. In CUP patients, the combined strategy of deep learning-predicted diagnosis and genetic mutations-based therapy could help to maximize the clinical benefit in a clinical setting and optimize the clinical development of innovative therapies.