bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential determinants of radiation-induced lymphocyte decrease and lymphopenia in breast cancer patients by machine learning approaches.
Authors: Yu Hao , Chen Fang , Yang Li , Jin Jian-Yue , Kong Feng-Ming Spring
Published: June 2021

e12567

Background: Radiation-induced lymphopenia accompanied with radiation therapy is associated with inferior clinical outcomes in a wide variety of solid malignancies. This study aimed to examine the potential determines of radiation-induced lymphocyte decrease and radiation-induced lymphopenia in breast cancer patients who underwent radiotherapy. Methods: Patients with breast cancer treated who underwent radiotherapy were enrolled in University of Hong Kong-Shenzhen Hospital (our cohort). Circulating lymphocyte levels were evaluated within 7 days prior to and end of radiation therapy. Feature groups including clinical data, tumor characteristics, radiotherapy dosimetrics, treatment regiments were also collected. We applied machine learning algorithms (Extreme Gradient Boosting, XGboost) to predict the ratio of lymphocyte level after radiotherapy to baseline lymphocyte level and the event of lymphopenia and compared with Lasso regression approaches. Next, we used Shapley additive explanation (SHAP) to explore the directional contribution of each feature for lymphocyte decrease and lymphopenia. For the purpose of model validation and proof-of-concept validation, an independent cohort of patients enrolled in prospective trial was eligible (IP cohort). Results: A total of 589 patients were enrolled in our cohort and 203 patients in IP cohort. XGboost models which trained in our cohort with performances of a mean RMSE: 0.157 and R2: 53.9% for the ratio of lymphocyte levels; a mean accuracy: 0.757 and ROC-AUC: 0.733 for the lymphopenia events, separately. These models can predict the ratio of lymphocyte levels with a mean RMSE: 0.175 and R2: 47%; predict the lymphopenia events with a mean accuracy: 0.739 and ROC-AUC: 0.737 in the totally independent IP cohort. The feature group of dosimetrics had the largest predictive power with RMSE: 0.192, R2: 29.8%, accuracy: 0.678 and ROC-AUC: 0.667; followed by the group of baseline blood cells with predictive power as RMSE: 0.207, R2: 18.9%, accuracy: 0.669 and ROC-AUC: 0.645. Next, by SHAP value analysis, we investigated that integral dose of the total body, V5 dose, mean lung dose and V20 dose of ipsilateral lung/bilateral lungs were in consequence important promote factors for lymphocyte decrease and for the event of lymphopenia, while the features of baseline monocyte, mean heart dose and tumor size played a role of protection at some extend. Conclusions: In this study, we constructed robust XGboost models for predicting the lymphocyte decrease and the event of lymphopenia in breast cancer patients who underwent radiation therapy. We also applied SHAP analysis for revealing the directional contribution of features. These results are important either for the understanding the contributions of dosimetrics on immune response or for the refine of radiation dosimetrics before treatment in future clinical usages.
Family history of breast and/or ovarian cancer (FHBOC) as an independent prognostic factor in triple negative breast cancer overall survival.
Authors: Rioja Patricia , Ruiz Rossana , Morante Zaida , Mantilla Raul , De la Cruz Ku Gabriel Antonio , Lujan-Peche Maria , Cotrina Jose Manuel , Fuentes Hugo , Neciosup Silvia P. , Gomez Henry Leonidas
Published: June 2021

e12579

Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.
Outcome of neoadjuvant treatment in triple-negative breast cancer in a rural underserved community.
Authors: Majer Martin , Little Elizabeth Fauchier , Jones Sarah , Dong Jasmine , Hutton David , Bezdickova Karolina , Tomanova Lucie , Promlap John , Promlap Tien , Schneringer Greg , DeMartini Steve , Russell Michael , Joyner April , Schmidt Susan , Nagubandi Ravi , Skau Randell , Swars Monica , Powell Megan , Ordorica Edward J.
Published: June 2021

e12608

Background: Complete pathological response (pCR) is a surrogate of successful neoadjuvant treatment of triple-negative breast cancer (TNBC). We extended our study from 2016, where we discussed unusually high pCR employing taxane/platinum (T/P) without the use of adriamycin and cyclophosphamide (AC). Methods: This is a retrospective observational study of an underserved, low income, rural population in Oroville, California over 10 years (2011-2021). Neoadjuvant chemotherapy was offered to eighteen women with ages ranging from 36 to 77 years old (mean age is 56). Minimum requirements for evaluation was three cycles administered within 90 days of starting treatment. The primary end point of this study was pCR. We analyzed the relationship between pCR, chemotherapy regimen, proliferation rate of original tumor by Ki-67 and the ratio of neutrophil and lymphocyte (NLR). The two regimens of chemotherapy included both standard AC+T or the alternative treatment with T/P. We grouped Ki-67 to above and below 50% pre-treatment. NLR was grouped between those above and below 3.2. Results: Our study produced a respectable response rate with 12/18 (67%) achieving pCR. There was no difference with or without exposure to anthracyclines. Out of the twelve who achieved pCR, eight (67%) received T/P and four (33%) got AC+T. Ki-67 in all eighteen patients ranged from 2% to 97% with a median of 75%. Ki-67 was >50% in 10/12 (83%) patients who achieved pCR and 3/6 (50%) in those who did not have a response. NLR was a significant predictor for pCR. 8/12 (67%) of patients who experienced pCR had a NLR of <3.2 compared to the 1/6 ( 17%) with no response. The p-value is .0455. Conclusions: Treatment with the alternative regimen of T/P didn’t affect pCR in our population. We hypothesize that some of the beneficial effects of cytotoxics affected the patient’s immunological milieu on top of the direct effect of the malignant clone.
Clinical and pathological response to neoadjuvant chemotherapy (NCT) in patients with triple-negative breast cancer (TNBC).
Authors: Krivorotko Petr , Zhiltsova Elena , Gigolaeva Larisa , Emelyanov Alexander , Pesotskiy Roman , Yerechshenko Sergey , Nikolaev Kirill , Komyahov Alexander , Ivanova Olga , Tabagua Tengiz , Zernov Konstantin , Ivanov Vadim , Aseeva Zalina , Bessonov Alexander , Semiglazov Vladimir
Published: June 2021

e12616

Background: Neoadjuvant chemotherapy (NCT), Triple-negative breast cancer (TNBC) including anthracyclines and taxanes for early stages of TNBC, allows to achieve pathological complete response (pCR) in 25-36% of patients. Pathological complete response (pCR) significantly correlates with an increase in disease-free survival (DFS) and overall survival (OS). Methods: Randomized, monocentric trial was conducted in NN Petrov National Medical Research Center of Oncology from 2016 to 2019. 99 patients aged from 28 to 68 years with confirmed TNBC were included in trial: 96 had invasive ductal carcinoma G3, 3 - metaplastic cancer, negative BRCA mutations (a test for Founder mutations was performed).Patients were randomized in 3 groups, depending on the NCT regimen:1st subgroup (24 patients) - Eribulin in combination with Carboplatin AUC 5 x 4 cycles 2nd subgroup (37 patients) - Paclitaxel in combination with Carboplatin AUC 5 x 4 cycles 3rd subgroup (38 patients) –Carboplatin AUC5 + Doxorubicin + Paclitaxel x 6 cycles. Patients 1 and 2 subgroups in an adjuvant mode received 4 cycles of AC. Results: Clinical complete response (cCR) by physical examination (palpation) was achieved in 44 out of 99 patients (44.4%). Clinical complete response (cCR) by ultrasound and MG - in 27 (27.2%) patients. Miller-Payne V regression stage was achieved in 55 out of 99 cases (55.6%). In clinical cT1-T2 stage (n = 70), ypCR was achieved in 49 cases (70%), cT3-T4 (n = 29) ypCR in 6 patients (20.68%). Before NCT, 71 patients had status cN0-N1. Conversion to ypN0 occurred in 57 patients (80.2%). In 28 patients with cN2-N3 status, conversion to ypN0 occurred in 7 patients (25%). The median follow-up was 58 months. Progression was observed in 15.1% of patients, mortality – 6%. Local recurrence - 6 patients (6%), all patients were with residual tumor after NCT. Distant recurrence – 8 patients (8.1 %). Local recurrence rate and distant recurrence rate did not correlate with type of surgery (BCS or ME), but correlated with ypCR. Conclusions: NCT for TNBC is advisable both for locally advanced breast cancer and early breast cancer BC. De-escalation of BC surgery is possible in the future, especially in cT1-T2 stage patients (n = 70) where ypCR rate reaches 70%. It is planned to continue the trial with the vacuum aspiration biopsy of the tumor bed and SLNB after NCT.SLNB after NCT is advisable only in cN0-N1 group of patients (n = 71), since conversion to ypN0 was achieved in 57 patients - 80.2%.
Survival outcomes of breast cancer patients with brain metastases: Single center experience from Northern India.
Authors: Sagiraju Hari Krishna Raju , Gogia Ajay , Sharma Dayanand , Deo S. V. S. , Mathur Sandeep
Published: June 2021

e13003

Background: Brain metastasis (BM) is a poor prognostic factor for survival among breast cancer (BC) patients. Very few studies reported in the literature have challenged this premise, suggesting that time to the occurrence of brain metastasis and the survival times following brain metastasis differ significantly between BC subtypes. The purpose of this study was to evaluate the clinico-pathological characteristics associated with brain metastasis free survival (BMFS), survival after brain metastases (SABM) and overall survival among Indian women with BC and BM. Methods: Among 621 patients treated for metastatic BC from 2015 to 2018 at All India Institute of Medical Sciences-New Delhi, 79 (12.7%) patients were identified to have BM. Of these ten individuals have presented with BM at the time of presentation. Survival analysis and Cox proportional hazards models were fitted to explore clinco-pathological factors that are associated with survival outcomes in these individuals. Results: Median age of the sample is 42 years (range:22-64). Triple negative breast cancers (TNBC) accounted for 25.3% and HER2 positive were 49.4% in our sample. Median time for the occurrence of BM from cancer diagnosis was 20.5 months (95% CI:14.7-26.2) in the overall sample, while among TNBC and HER2 positive tumors was 14.1 and 20.6 months respectively. In Cox multivariable model, T4stage [Hazard Ratio (HR) (95%CI): 2.4(1.1-5.3)], having a metastatic disease other than to brain at the time of presentation [HR(95%CI): 2.8(1.5-5.4)] and TNBC [HR(95%CI): 2.7(1.1-6.7)], was observed to be significantly associated with BMFS. Median SABM was 7.9 months (95% CI 5.2–16.2) and the median overall survival from the cancer diagnosis was 32.4 months (95% CI 23.4–40.8). Adjusted for age, only the presence of multiple brain lesions (>2) was significantly associated with SABM [HR (95%CI): 2.4(1.1-5.2)]. However, TNBC [HR (95%CI): 2.9(1.2-7.4)]and baseline metastatic disease [HR (95%CI): 2.2(1.2-4.2)] were significantly associated with overall survival following cancer diagnosis in these individuals. HER2 positivity was not associated with BMFS or SABM in this cohort. Conclusions: In this single-institutional study, clinical T4 stage, TNBC subtype and baseline metastatic disease have shown to be significantly associated with BMFS and overall survival. These results suggest that women in Indian population with these baseline clinico-pathological characteristics at the diagnosis of breast of cancer should be frequently monitored for BM.
Trastuzumab biosimilar (Kanjinti) in breast cancer patients: One-center retrospective observational study.
Authors: Jagiello-Gruszfeld Agnieszka I. , Lemanska Izabela , Brewczynska Elzbieta , Pogoda Katarzyna , Dubianski Roman , Sienkiewicz Renata , Szombara Ewa , Jagielska Beata , Nowecki Zbigniew
Published: June 2021

e13015

Background: The switch of anti-HER2 therapy from the reference drug Herceptin to a biosimilar has presented challenges to the clinics. Real world data on trastuzumab biosimilars are very limited or not available. In our clinic we perform observational retrospective study to confirm safety and efficacy Kanjinti. Methods: 195 patients (pts) with HER2-positive breast cancer were treated with Kanjinti from Jul.18. 2018 to Jan.29.2020. Cardiac events (↓LVEF) and other unexpected or serious adverse events were monitored in all pts. 34 pts received carboplatin, docetaxel pertuzumab and trastuzumab biosimilar in neoadjuvant setting, 99 received trastuzumab biosymilar in monotherapy or with other cytostatic drugs in neoadjuvant or adjuvant setting, and 62 received docetaxel, pertuzumab and Kanjinti in metastatic setting. Results: Pertuzumab was used in combination with Kanjinti in 49% of pts (32% in the 1st. line of palliative tretment and 17% in the neoadjuvant settings, respectively).Switching from Herceptin to Kanjinti was observed in 65% of MBC patients and 37% of EBC patients. Switching was done at a median of 4th cycle. 6 patients had a decline in LVEF. No other trastuzumab related adverse events was observed. Conclusions: The management of HER2 positive breast cancer in our clinic follows the international recommendations. This is the first real world safety data of Kanjinti from Poland. The 12-month follow-up treatment with Kanjinti an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Kanjinti or Kanjinti combined with pertuzumab, the safety profile was similar to that previously reported in other studies.
Patients’ perceptions of care coordination among NCORP therapeutic clinical trial participants: A matched case-control study.
Authors: Okado Izumi , Pagano Ian , Rhee Jessica , Berenberg Jeffrey L. , Holcombe Randall F.
Published: June 2021

e13504

Background: Effective coordination of care (CC) is a critical component of high-quality cancer care; however, many patients with cancer continue to receive poorly coordinated care. CC experiences among therapeutic clinical trial (CT) participants are relatively unknown. We examined cancer patients’ perceptions of CC among CT participants using a validated Care Coordination Instrument (CCI). Methods: The study sample (N = 90) consisted of 45 CT participants and 45 matched non-participants from archival data from our prior CC studies. 171 patients who participated in therapeutic cancer clinical trials through the Hawaii Minority/Underserved NCI Community Oncology Research Program (NCORP) between 2015 and 2020 were contacted for study participation, and 26% completed the CCI. The CCI measures overall perceptions of CC and across 3 domains (Communication, Navigation, Operational). Paired t-tests were used to compare overall and domain scores between CT participants and non-participants. The two groups were matched by age, gender, cancer type (breast, GI, other), and clinical stage. Results: Among CT participants, the mean age was 61.7 ( SD = 9.4), and the majority were female (67%) and Asian (56%). The most common cancer types were breast (27%) and GI (16%), with 24% with stage III disease. CT participants reported significantly higher total CC scores than non-participants (62.5 vs. 55.8; p = .0008). Similar trends were found for Navigation ( p = .007) and Operational ( p = .001) domain scores. 29% of CT participants reported receiving high-intensity CC assistance from their clinical research associates (CRAs), and 27% indicated receiving moderate-level CC assistance. Responses to open-ended questions regarding CC revealed that CT participants received assistance with a variety of CC activities from their CRAs, including scheduling appointments and explaining test results and procedures. Conclusions: Patients who participate in therapeutic cancer clinical trials report more positive perceptions of CC compared to non-participants. Qualitative data suggest that significant care coordination support is provided by the clinical research associate. The results underscore the importance of CC support provided by CRAs who may be an unrecognized component of the healthcare delivery team. CC provided by CRAs may contribute to improved quality and value of cancer care for patients enrolled on therapeutic clinical trials.
Encouraging teamwork and innovative practices by creating proximity: A qualitative study of continuous improvements in the Quebec Cancer Network.
Authors: Tremblay Dominique , Touati Nassera , Usher Susan , Cournoyer Johanne
Published: June 2021

e13509

Background: Quality cancer care relies on each profession keeping up with advances and best practices and spreading these across a complex multi-team system1. It requires enabling multiple providers and people living with cancer to bridge the distance between them and complement each other's contributions. The proximity framework2 provides a valuable way to understand conditions that increase the likelihood of knowledge sharing, innovation and collaboration. Methods: A qualitative study design of the Quebec Cancer Network was undertaken, with data collected from interviews with policymakers, managers, providers and users (N=22), observation of national and local level meetings (N=28) and document review. Interpretive Description using content analysis sought to identify actions that created proximity dimensions and the perceived influence these had on the development and spread of new approaches. Results: Deliberate actions taken within the network created different dimensions of proximity that impacted teamwork. Prescriptions from network leadership – including consistent promotion of the National cancer plan, patient participation in governance structures, shared quality indicators, and establishment of multidisciplinary committees at local level, created cognitive proximity: a shared mental model emphasizing patient-centred care and organizational proximity: shared standards across the network. Support for professional communities of practice created relational and institutional proximity, increasing trust and knowledge sharing. Local committees enhanced relational and cognitive proximity as providers came to appreciate and optimize each other's contribution to care. Conclusions: The combination of proximity dimensions created through communities of practice and prescriptions from the national level help develop and spread improvements that are tailored to - and take advantage of - networked team-based cancer care delivery. This reflects a balanced proximity where communities of practice pursue new knowledge and innovative practices that can be introduced in local committees to see how it fits with other contributions to solving a problem, thereby promoting recognition of interdependency within and between teams. Synergy between actions is essential to enhancing proximity. The proximity framework offers a complementary perspective to better understand opportunities for improving models of care. References: 1Weaver, S. J., et al. (2018). Unpacking care coordination through a multiteam system lens. Medical care, 56(3), 247-259. et al. Unpacking Care Coordination Through a Multiteam System Lens. Medical Care. 2018;56(3):247-59. 2Knoben, J., & Oerlemans, L. A. (2006). Proximity and inter‐organizational collaboration: A literature review. I nternational Journal of management reviews, 8(2), 71-89.
New drug approvals and their effect on performance for participants in the Oncology Care Model.
Authors: Bilbrey Larry Edward , Schleicher Stephen Matthew , Chaudhry Basit Iqbal , Yue Andrew , Blakely L. Johnetta
Published: June 2021

e13525

Background: The Oncology Care Model (OCM) is an oncology-specific value-based care model that holds participating practices accountable for all costs of care. Medicare implements quantitative adjustments to model target costs in OCM, including a trend factor to reflect aggregate cost growth and a novel therapy adjustment for new indications. However, it is unclear how well these adjustments account for the emergence of new therapies that are evidence based and influence standard of care for an individual cancer type. We sought to investigate this by studying the impact that FDA approval for brentuximab vedotin (BV) in the first line setting in March 2018 had on OCM practice performance in Hodgkin’s Lymphoma (HL). Methods: We identified all HL OCM episodes attributed to Tennessee Oncology (TO), a large community oncology network of over 90 oncologists, during performance periods (PP) 3 through 6. HL episodes within the lymphoma bundle were identified through the use of individual ICD-10 coded diagnoses on claims for antineoplastic infusions and E&M visits. Using OCM performance data, our electronic health record, and claims data analytics software, we calculated average episode target costs, drug spending by drug type, and hospitalization costs to determine key determinants of OCM performance. Results: During the study period, there were 577 episodes of lymphoma attributed to TO, of which 28 were for patients with HL. TO’s OCM performance in HL was significantly under target in PP4 (under target by $13.5K) and significantly over target in PP5 (over target by $32.1K) after the updated BV FDA approval. Average episode spending on BV increased by over $45K during this timeframe, while OCM target cost increased only by approximately $19K. Despite the change in OCM performance, hospitalization costs and hospice utilization remained relatively stable. Conclusions: In the OCM, despite quantitative payment factors that in principle are intended to adjust target prices to reflect changing cost dynamics, significant gaps exist. These gaps can inappropriately shift risk to providers for the appropriate use of new indications, including those that change standard of care. The example of brentuximab vedotin in HL illustrates the difficulty in reaching performance benchmarks due to dynamics associated with the rising cost of drugs. Further methodological changes are needed in future oncology value-based care models to ensure accurate prediction of rapidly changing treatment costs for appropriate therapies. Hodgkin’s lymphoma OCM payment period cost and utilization comparison data.[Table: see text]
Cancer care system strengthening (Pendharkar model) offers uninterrupted care continuum during COVID19 pandemic.
Authors: Pendharkar Dinesh , Tripathi Chandramauli
Published: June 2021

e13540

Background: District cancer care programme is operational in more than 150 districts of India. This programme has created nodal cancer units n government run district general hospitals offering cancer related services including chemotherapy and palliative care. During pandemic (COVID19), due lockdown, cancer patients were not able to access tertiary level specialised cancer centres. Aim of this presentation is to reaffirm the necessity of health system strengthening at peripheral level. Methods: With the aim of decentralization and task shifting, district cancer care programme is being implemented in 8 states of India. One general duty medical officers and paramedical staff is trained to assist cancer patients. The physician work under 24 x7 mentorship of oncology team. The government has created a physical cancer care unit with availability of some essential chemotherapy drugs as well. Cancer patients can access these units for assistance in diagnostics, follow-up, toxicity care, chemotherapy and palliative care. Results: We analysed data from few districts in year 2020. The number of patients vesting the units showed an increase during months of total lockdown. Data from 14 districts were analysed. It shows that number of outpatient visits and chemotherapy sessions were higher during strict lockdown. From January 2020 to December 2020 there were 19,273 outpatient visits, and 9,788 inpatient visits. During months of a strict lockdown-March, April, May, June the number increased.7,729 sessions of chemotherapy were performed and more than 2,230 new cases were registered during this year. Conclusions: The pandemic has brought new challenges and has compelled us to learn ways of care continuum. The most important has been the necessity of decentralisation of specialised care, its evenly and equitable distribution. District cancer care programme, as a measure of health system strengthening, which is being evolved in India has further emphasized the importance of such a system building.
Characteristics of the Multi Disciplinary Cancer Conference (Tumor Boards) in the COVID 19 era.
Authors: Simpson Lijo , Mathew Anju , Wojciechowski Robert
Published: June 2021

e13561

Background: Cancer centers in the US are required to discuss a minimum of 15% analytic cases and prospective presentation (minimum 80%) in the multidisciplinary case conference (tumor board, MDCC), per the Commission on Cancer accrediting standards. Tumor board discussion have been shown to improve treatment decision making and patient outcomes. These meetings were in person meetings in the Pre-COVID era. The COVID 19 pandemic and the subsequent requirements for social distancing forced hospitals to move most MDCCs to a virtual format. We report on the large scale utilization of a propriety Care-Coordination platform OncoLens to run MDCCs across the country. Methods: Technology quality metrics were collected from the ongoing daily usage of the platform including time characteristics, care team utilization metrics, average attendance, quality metrics collected for accreditation and clinical trials matching on the OncoLens platform. Results: The virtual platform was accessible to around 8000 providers across the United States. On average per month there were 250 virtual meetings with over 290,000 meeting minutes. Conferences ranged from 30 minutes to 4 hours. 75% of users used the web application 25% of users utilized their smart phones .System uptime was 99.99%. Hospitals were able to conduct General and Site specific conferences. Virtual attendance of the required specialties of Medical Oncology, Radiation Oncology, Surgery, Pathology and Radiology was attained, with the average conference attendance being 14. On average hospitals required 2 administrative training sessions. Most of the case presentations were prospective. This format does enable cancer programs to collect quality metrics around Cancer program accreditation by the American College of Surgeons. A wide variety of common and rare cancer types were discussed in the virtual format. 66% of patients discussed potentially matched to clinical trials during the discussion. Conclusions: The shift of MDCCs to a mostly virtual environment occurred quickly in response to the COVID 19 pandemic. It took an average of 2 training classes to get the cancer care team on board with the use of new technology. It is possible to have high quality discussions and attain metrics for Commission On Cancer accreditation utilizing a virtual platform.
Cooperative group and pharmaceutical sponsored clinical trials: Perceptions of U.S. community oncologists.
Authors: Swain Richard Scott , Zettler Marjorie E. , Jeune-Smith Yolaine , Feinberg Bruce A. , Gajra Ajeet
Published: June 2021

e13571

Background: Many community-based oncologists in the US participate in clinical trials. These trials largely fall into two categories: trials run by cooperative (co-op) groups, funded and supported by the National Cancer Institute and trials developed, and supported by the pharmaceutical (pharma) industry. This study aimed to assess participation in, and perceptions regarding, co-op versus pharma trials among US community oncologists. Methods: We invited healthcare providers (HCP) across the continental US to attend 4 virtual meetings held between September and November 2020. Participants submitted their demographic information and responses to targeted questions regarding their opinions about co-op- and pharma-sponsored trials via a web-based pre-meeting survey. We evaluated participant HCP practice demographics and survey responses using descriptive statistics. Results: Of 259 surveyed participants, HCPs specialized in hematology-oncology (57%) and medical oncology (40%) with mean (median) 19 (18) years’ clinical experience. Most HCPs (178; 69%) reported participating in clinical research, and of these, 137 (77%) participated in co-op-led and 156 (88%) participated in pharma-led clinical research. HCPs preferred participating in both pharma and co-op (49%), pharma only (22%), and co-op only (11%) trials, while 18% preferred not to participate. Co-op trials were considered more prestigious to lead (86%), less likely to imply a conflict of interest (59%), and to address more pertinent questions (58%), while pharma trials had perceived advantages of better compensation (61%) and superior efficiency (48%). Co-op trials were perceived as not being financially sustainable (69%) and slower to accrue patients (85%) than pharma-led trials. Relatedly, in a hypothetical scenario of competing trials with identical design, the majority (60%) of HCPs preferred enrolling a loved one in a co-op trial. HCPs practicing in facilities with academic affiliation (34%) and in non-academic (66%) settings reported similar perceptions about co-op- and pharma-led trials; though, HCPs in academic settings were more likely to participate in clinical research compared to those in non-academic settings (82% vs. 62% [ P=0.001], respectively). Conclusions: In our survey of experienced HCPs, co-op-led clinical trials were perceived generally more favorably than pharma-led trials, even with concerns regarding cost, feasibility, and slower recruitment. However, despite their preference for co-op trials, HCPs were more likely to participate in pharma-led trials. Almost a third of surveyed HCPs are not participating in clinical trials and a fifth do not wish to. These findings can inform stakeholders (co-op trial leadership, pharma drug development teams, and patient advocacy groups) regarding appropriate education, design, and messaging regarding future clinical trials in oncology.
Implementation of the Vinehealth application, a digital health tool, into the care of patients living with brain cancer.
Authors: Gvozdanovic Andrew , Mangiapelo Riccardo , Patel Rayna , Kirby Georgina , Kitchen Neil , Miserocchi Anna , McEvoy Andy , Grover Patrick , Thorne Lewis , Fersht Naomi , Williams Norman R. , Marcus Hani , Kosmin Michael
Published: June 2021

e13582

Background: Cancers of the brain lead to significant neurocognitive, physical and psychological morbidities. Digital technologies provide a novel platform to capture and evaluate these needs. Mobile health (mHealth) applications typically focus on one aspect of care rather than addressing the multimodal needs of the demographic of these patients. The Vinehealth application aims to address this by tracking symptoms, delivering machine learning-based personalised educational content, and facilitating reminders for medications and appointments. Where mHealth interventions traditionally lack the evidence-based approach of pharmaceuticals, this study acts as an initial step in the rigorous assessment of a new digital health tool. Methods: A mixed methodology approach was applied to evaluate the Vinehealth application as a care delivery adjunct. Patients with brain cancer were recruited from the day of their procedure ± 7 days. Over a 12-week period, we collected real-world and ePRO data via the application. We assessed qualitative feedback from mixed-methodology surveys and semi-structured interviews at onboarding and after two weeks of application use. Results: Six participants enrolled of whom four downloaded the application; four completed all interviews. One patient set up their device incorrectly and so couldn't receive the questionnaires; excluding this patient, the EQ-5D-5L and EORTC QLQ-BN20 completion rates were 100% and 83% respectively. Average scores (±SD) at onboarding and offboarding were EQ-5D-5L: 2.07±1.28 and 1.73±1.22, and QLQ-BN20: 13.33 and 22.5. In total: 212 symptoms, 174 activity, and 47 medication data points were captured, and 113 educational articles were read. Participants were generally optimistic about application use. All users stated they would recommend Vinehealth and expressed subjective improvements in care. Accessibility issues in the ePRO delivery system which impacted completion rate were identified and have subsequently been fully addressed. Conclusions: This feasibility study showed acceptable patient use, led to a subjective improvement in care, and demonstrated effective collection of real-world and validated ePRO data. This provides a strong basis to further explore the integration of the Vinehealth application into brain cancer care. This study will inform the design of a larger, more comprehensive trial continuing to evaluate improvements in care delivery through data collection, educational support and patient empowerment.
A nurse-led telephone triage for the prevention and control of COVID-19 spread in an oncology department.
Authors: Calvetti Lorenzo , Simionato Francesca , Cappetta Alessandro , La Russa Francesca , Cimenton Roberta , Gasparin Barbara , Corà Francesco , Aprile Giuseppe
Published: June 2021

e13617

Background: After the results of the Nurse-led Telephone Triage (NTT) study ( Calvetti L, et al. ASCO 2020), the system has been implemented to prevent unnecessary hospitalizations of cancer patients. With the pandemic outbreak, a dedicated SARS-CoV-2 2019 (COVID-19) NTT protocol was added to monitor cancer patients (CPs) receiving active medical treatment. We report on the impact of NTT in limiting accesses and minimizing the risk of spread of the infection through the Department of Oncology. Methods: CPs on active medical treatment were educated to call the NTT in case of any symptoms suspected for COVID-19 infection to the Oncology Department of Vicenza, Italy, during the COVID-19 pandemic (February 22 2020 to January 31, 2021). Each event assessment was performed by trained oncology nurses with the supervision of a medical oncologist on duty and in case of suspected COVID-19 infection a testing pathway for COVID-19 was activated. Primary endpoint of this study was to compare incidence of COVID-19 and related deaths in both CPs on active medical treatment and health workers with the rate in the overall population of Veneto region. Results: From February 22 2020 to January 31, 2021 1,154 patients received systemic anticancer treatment (versus 1,022 patients in the same 2019 – 2020 period). Total consultations at NTT were 587; 97 patients reported symptoms suspected for COVID-19 infections. The COVID-19 testing pathway was launched in 60 CPs and a positive test was reported in 25 CPs (2.2% incidence compared to 6.5% in the overall Veneto region population). Two COVID-19 related deaths were reported (8% death rate). In the same period, 2/54 (3.7%) health workers tested positive for COVID-19. Patients who tested positive had a median treatment delay of 25 days. Conclusions: The NTT system in the clinical practice provided a useful tool for monitoring and limiting hospital-acquired COVID-19 infection among both CPs on active treatment and health workers.
Comparing implementation of Telemedicine compliance and feasibility among oncology patients across countries during the COVID 19 pandemic.
Authors: Pelles Sharon , Peleg Hasson Shira , Waissengrin Barliz , Hasid Lior , Deutsch Irad , Safra Tamar , Wolf Ido , Geva Ravit
Published: June 2021

e13622

Background: COVID19 pandemic expedited the use of telemedicine across nations. Oncology patients as at risk population especially needed the use of telemedicine to continue patient care. Evaluating patients' compliance and satisfaction with telemedicine is needed and might vary across nations and cultures. Experience from telemedicine during COVID might help shape oncology care in the future. Methods: A questionnaire that was locally validated in the Tel-Aviv Sourasky Oncology Division was distributed internationally using the BELONG.life digital health platform, a free and anonymous application (app) for cancer pts and caregivers. Results were compared between US pts replied through the app and Israeli patients. Results: The questionnaire was distributed to 232 Israeli patients and to 362 BELONG users in the US. The compliance was 74% and 35% pts respectively. Majority of users in Israel were male (54%) versus female in the US (77%). In the US 75% were Caucasian. More Israeli patients had a family member present in the call then in the corresponding US group (47% vs 64%). Both Israeli and US pts felt satisfied with the meeting and reported the willingness to continue with the same approach in the future regardless of the pandemic situation (84.9%, 63%, respectively). 95.9% of Israeli patients were attended by their regular doctor as opposed to 71% in the US. Call time duration was prolonging to 30-60 min and willingness to repeat the calls dropped to 47% when performed with a different doctor. In the US 76% of patients reported the telemedicine call saved them precious time. Conclusions: Patients' response to telemedicine meetings across countries was positive with oncology care visits being maintained successfully despite the ongoing COID19 pandemic. Most patients regardless of country of origin showed willingness to continue with telemedicine however maintaining the care with the patient's regular physician is important for the continued use of telemedicine in reducing visits time and improving the pts interaction and satisfaction. Clinical trial information: 0227-20.
The analysis of EGFR variants in Chinese adult glioblastoma patients.
Authors: Li Qiao , Sun Weijie , Lu Yi , Guo Didi , Han Tiantian , Lu Guanghua , Li Xiaomin , Ding Ran , Bu Fanfeng
Published: June 2021

e14020

Background: Glioblastoma multiforme (GBM) is the most common primary brain tumor with complex genetic alterations and genomic profiles. EGFR amplification occurs in approximately 40% of primary GBM，EGFR mutation is also a prevalent genetic abnormality in GBM. A series of potential therapies targeting EGFR variants are currently in development, such as tyrosine kinase inhibitors (TKIs), monoclonal antibodies, vaccines, etc. However, to date, EGFR-targeted therapy continues to face significant challenges. A deeper understanding of EGFR variant profiles and pathobiology of GBM will be required. Methods: Next-generation sequencing of 131-gene profiling was performed to analyze EGFR activating mutations from 891 Chinese glioma patients in 2019-2020. Somatic mutations and copy number variations were detected following the standard operating procedure (SOP). We screened out the EGFR activating mutation and calculated the mutation frequency and the tumor location. Results: 51 GBM patients had activating mutations. The average age was 49 years (range,25-73 years). Most of the tumors occurred in the cerebral hemisphere (56.9%), followed by ventricles (3.9%) and thalamus (3.9%), etc. 43/51 (84.3%) were accompanied by high-fold EGFR amplification. 9/12 (75%) were EGFR intracellular mutation occurs with EGFR amplification, 31/35 (88.6%) were EGFR extracellular mutation occurs with EGFR amplification. Moreover, 4 patients carried EGFR intracellular and extracellular mutation occurs with EGFR amplification. There was no significant difference between the ratio of intracellular mutations and extracellular mutations with EGFR amplification (P=0.3496). Conclusions: In our GBM patients, EGFR activating mutations were accompanied by high-fold EGFR amplification. As we know that, GBM benefit from EGFR-TKIs may be limited. Therefore, multi-targeted combination therapy research could be considered in the future.
MAPK pathway alteration may be a new integrated diagnosis term.
Authors: Cheng Chuandong , Ji Ying , Han Tiantian , Li Xiaomin , Huang Yahui , Sun Weijie , Lu Guanghua , Deng Wanglong , Ding Ran , Bu Fanfeng
Published: June 2021

e14022

Background: The 2016 CNS WHO classification is the first to include molecular factors to classify in glioma. We are in the age of glioma subgroups, in which the category depended on the histological and molecular composition, providing more clinical behavior, prognosis, and therapeutic targets hints. The most well-known molecular modifications are IDH1/2 mutation, ATRX variant, TP53 variant, BRAF mutation or fusion, 1p/19q co-deletions. However, there is a diagnostic term“NOS” in the 2016 CNS WHO classification，which indicates that a tumor could not be placed into a more specific WHO category. Here, our analysis of the MAPK pathway may suggest a new subtype. Methods: Targeted next-generation DNA sequence of the 131-genes panel was performed on gliomas in 119 patients. We measured the somatic variations in the MAPK pathway after filtering known driver mutations. The analysis of genomic alterations was performed using a two-sided Fisher exact test. Results: 90/119（75.6%）were excluded due to known driver mutations. 29/119(24.4%) were classified in NOS with a typical “single MAPK pathway alteration” and different histological characteristics and WHO grade. The median age at diagnosis was 35 years (4-79) in our gliomas. The most frequent mutations were NF1(10/29), FGFR1(7/29), KRAS (6/29), BRAF (3/29), PTPN11(2/29), although there are other gene mutations like FGFR2, FGFR3, AKT1, MAP2K1. According to cIMPACT-NOW update 4, our pediatric gliomas ( < 30 years, n = 14) could be identified as “diffuse glioma, other MAPK pathway alteration.” Our adult gliomas have a higher frequency of NF1 mutations（8/15 vs. 2/14, p = 0.05), a lower KRAS (1/15 vs. 5/14) and FGFR1 (2/15 vs. 5/14) mutations than children. Conclusions: Our result suggests that MAPK pathway alteration may be a new integrated diagnosis term in all ages of glioma. Moreover, KRAS and FGFR1 may be associated with pediatric gliomas. NF1 is more common in adult gliomas.
RBM8A promotes growth and invasion through the Notch/STAT3 pathway in glioblastoma.
Authors: Lin Yan , Zhang Jinyan , Hu Beiquan , Qin Gang , Liang Rong , Lin Yingying , Wei Jiazhang , Qian Zhongrun , Zou Donghua
Published: June 2021

e14038

Background: Glioblastoma (GBM) is a prevalent brain malignance with an extremely poor prognosis, which is attributable to its invasive biological behaviors. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the implication of RBM8A in glioblastoma progression remains unclear. Methods: Glioblastoma (GBM) data set was downloaded from the Cancer Genome Atlas (TCGA). Differential expression analysis was used to screen the differentially expressed genes (DEGs) between GBM and control, RBM8A high and low expression samples, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene Genomes (KEGG) analysis were performed on the co-upregulated DEGs. Additionally, We investigated the expression levels of RBM8A in 94 glioblastoma patients and explored the correlation between the RBM8A expressions with prognosis. Using in vitro and in vivo assays, we addressed the functional impacts of RBM8A on and the underlying mechanisms through which RBM8A contribute to glioblastoma progression. In addition, a comprehensive regulatory network of RBM8A regulation was constructed based on STRING database. Molecular docking model was used to predict the possibility of RBM8A binding to target genes. Combined with TCGA and Chinese glioma genome map (CGGA), gene set variance analysis (GSVA) was used to calculate the GSVA scores of the genes involved in the mechanism. Receiver operator characteristic curve (ROC) curve analysis and survival analysis were performed to explore the prognostic and diagnostic ability of GSVA score for GBM. Results: Our results indicate that higher RBM8A expression in glioblastoma tissues was associated with a poor prognosis. In addition, functional enrichment analysis based on genes related to RBM8A expression showed that RBM8A was related to cell cycle and Notch signaling pathway. RBM8A may promote glioblastoma cell proliferation and migration by activating Notch/STAT3 pathway in glioblastoma cells. In vitro and in vivo assays confirmed that knocking down RBM8A inhibited glioblastoma progression and invasion ability. We also observed that the pro-oncogenic effects of RBM8A in glioblastoma tissues were mediated by activation of the Notch/STAT3 pathway. Finally, it was concluded that the GSVA score has good diagnostic and prognostic value for GBM. Conclusions: RBM8A may promote glioblastoma cell proliferation and migration by activating Notch/STAT3 pathway in glioblastoma cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of glioblastoma.