bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival outcomes with immune checkpoint inhibitors (ICI) in metastatic uveal melanoma (MUM).
Authors: Lee Cha Len , Walsh Naomi , Keane Fergus , Lynch Emer , Reddan Tadhg , Craig Helen , O'Meara Aileen , Smith Deirdre , O'Neill Valerie , Horgan Noel , Kennedy Susan , Gullo Giuseppe , Crown John 
Published: June 2021

e21585 Background: The treatment of MUM remains highly unsatisfactory. Single agent ICI produce low response rates. Two recent phase II trials of combination Ipilimumab and Nivolumab yielded response rates of 12% and 18%. We report the long-term survival results of MUM patients (pts) treated with ICI in our institution. Methods: We conducted a retrospective analysis of all pts with a diagnosis of MUM in St Vincent’s University Hospital. Overall survival (OS) was calculated from time of first systemic relapse to death or latest follow-up. One-way ANOVA is used with p < 0.05 considered statistically significant. Results: Out of 244 pts with UM registered in our clinics between April 2008 to October 2020, 52 developed MUM. Median age at initial diagnosis 63 years. 26(50%) are females. Median duration of follow-up of the MUM pts is 35.1 months [2.71-123.2]. Median duration of follow-up from initiation of ICI therapy is 9.1 months [1.6-84.2]. First sites of metastases: liver only 71%, liver plus extrahepatic 17%, and extrahepatic only 12%. Fifteen pts (29%) underwent radical metastasectomy as initial treatment. Thirty-seven (71%) had non-resectable MUM and received systemic treatment (23 total: ICI = 18, chemotherapy = 4, BRAF inhibitors = 1), non-surgical locoregional therapies (5 total: chemosaturation = 3, radiofrequency ablation = 2) or supportive/palliative care (9) as first-line. An additional 22 pts received ICI as second or subsequent treatment, for a total of 40 treated with ICI. Of these, 17 received single agents ICI (Ipilimumab = 11, Pembrolizumab = 6), 13 received sequential Ipilimumab and anti-PD1, and 10 received combination Ipilimumab /Nivolumab. At the time of analysis on 31st October 2020, 9 out of 52 pts (17%) are alive at 2.6, 5.0,5.4,8.9,17.3, 54.7, 77.5, 83.1 and 121.7 months (the 6 longest all had ICI). The median OS is 14.3 months [0.6-121.7]. Pts treated with ICI demonstrated longer OS than pts who did not receive ICI [15.0 months, 5.0-121.7 vs 7.2 months, 0.6-34.6; p = 0.089]. The median OS is 24.9 months (sequential Ipilimumab and anti-PD1) vs 15.0 months (combination Ipilimumab/Nivolumab) vs 13.4 months (single agents). Of the three pts remain alive > 5 years, one is currently disease-free. Conclusions: Prolonged survival beyond five years is achieved by a minority of pts with MUM who receive ICI during their treatment history, although durable initial ICI-induced remission is very rare. Our data suggest that pts who receive two ICI drugs during their illness may have longer survival compared to those who receive only a single ICI.
The importance of variants of unknown significance (VUS) in BRCA mutation.
Authors: Mullai N 
Published: June 2021

e22507 Background: Genetic testing of patients for BRCA mutation may report variants of unknown significance (VUS). The use of multi-gene panels in clinical care has been increasing. Consequently, the reporting of variants of unknown significance has also increased. More than two decades of research and testing have elevated the status of BRCA1 and BRCA2 genes as the most well characterized genes. However, VUS are found even in BRCA1/2 testing. This raises many ethical and policy issues including communicating the significance of the results and possible clinical management options to patients. The practicing physicians would face the ethical and potential legal burden of contacting and explaining to patients, when any role of VUS changes and gets reclassified as potentially harmful. Methods: Data were collected retrospectively from medical records of patients tested for BRCA mutations. The results of fifty-two patients were analyzed. Eight patients had BRCA1 and BRCA2 mutations and twelve patients had variants of unknown significance. Results: When the results of thirteen patients with BRCA mutations with VUS were analyzed further, the variants included POLE, CHEK2, PALB2, MUTHYH, BR1P1, MSH3, ATM, RAD51C, GALNT12, etc. The age of these patients ranged from 39 years to 69 years. Four patients had ovarian cancer and eight patients had breast cancer, and one patient had both breast and ovarian cancers. The number of patients with stage IV, III, II, and I diseases were six, one, two, and two respectively. One patient had bilateral breast cancer and one patient had carcinoma in-situ. Eight patients had family histories of various cancers, including cancers of the breast, uterine, and prostate cancer. All patients were treated appropriately and three patients died due to their disease. Conclusions: Based on patients’ age, family histories, and disease characteristics BRCA mutation analyses were done. All patients tested positive for BRCA mutations and VUS were informed about their results. Variants of BRCA1 and BRCA2 occur in 2%-4% of tests depending on the laboratories, where the tests were performed. There is no concordance as to how VUS results were reported. There is conflicting evidence regarding the pathogenicity of VUS. These make clinical recommendations very complex. Based on existing guidelines, physicians can explain the details of the significance of BRCA! And BRCA2 mutations to patients with clarity. However, it is difficult and unclear to give recommendations regarding prophylactic measures, specific treatment options for BRCA mutation positive breast and ovarian cancer, follow-ups, and family testing in patients with VUS. Therefore, during BRCA testing, when VUS are reported routinely along with mutations of known significance, the treating physicians would need a better guidance to advise their patients without unduly increasing their anxiety, fear, and potential for misunderstanding.
Oncologist management of NTRK fusion-positive NSCLC improves after virtual patient simulation participation.
Authors: Worst Michelle Arielle , Cain Brittany , Nelson Tipp , Cohen Jacob , Drilon Alexander E. 
Published: June 2021

e23008 Background: Although relatively rare, neurotrophic receptor tyrosine kinase (NTRK) fusions, represent a clinically relevant subgroup of NSCLC that can derive benefit from targeted therapies. Relatively quick and durable responses have been achieved with these targeted therapies in advanced NSCLC and intracranial activity has also been observed. The objective of this study was to determine if an online, virtual patient simulation (VPS)-based continuing medical education (CME) intervention improved performance of oncologists in using appropriate strategies to diagnose and manage patients with NTRK fusion-positive advanced NSCLC. Methods: The CME intervention consisted of two patient cases presented in a VPS platform that allowed learners to order lab tests, diagnoses and treatments in a manner matching the scope and depth of actual practice. Clinical decisions made by the learners using open field entries within an EHR interface were analyzed and, after each decision, tailored clinical guidance (CG) was provided based on current evidence and expert recommendation. Learner decisions were collected post-CG and compared with each user’s baseline (pre-CG) data using a McNemar’s test to determine P values. Results were then aggregated for the two cases based on clinical decisions and stratified by practice setting. The activity posted July 31, 2020; data were collected through December 1, 2020. Results: Overall significant improvements were seen after CG in clinical decisions made by oncologists in both the community and academic settings [reported as % absolute improvement (% correct pre-CG vs % correct post-CG); P value]. Conclusions: This analysis demonstrated that VPS that immerses and engages oncologists in an authentic and practical learning experience can significantly improve evidence-based clinical decisions related to the diagnosis and management of patients with NTRK fusion-positive advanced NSCLC. Despite the improvements, additional educational activities are needed to address any residual gaps and further increase oncologists’ ability in this clinical setting.[Table: see text]
Refining the approach to patients with primary soft tissue sarcoma of the extremities and trunk wall (ESTSTS): Outcome improvement over 30 years at a single institution.
Authors: Danieli Maria , Barretta Francesco , Fiore Marco , Radaelli Stefano , Sangalli Claudia , Barisella Marta , Stacchiotti Silvia , Palassini Elena , Miceli Rosalba , Callegaro Dario , Casali Paolo Giovanni , Gronchi Alessandro 
Published: June 2021

e23548 Background: In 2011 we reported the improved outcome of ESTS pts treated between 1987 and 2007 at Istituto Nazionale Tumori (INT), Milan (Italy). We updated the analysis at a later follow-up (FU) to assess possible changes in survival of ESTSTS. Outcomes according to histology were also explored. Methods: Pts with primary localized adult-type ESTSTS surgically treated at INT between 1987 and 2017 were retrospectively reviewed and divided into 6 groups according to the date of primary surgery. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local relapse (LR), distant metastases (DMs) were calculated for each group in a competing risks framework. DM free survival (DMFS) was calculated for each group taking into account all DMs (occurred as first or later). PostDM survival and all outcomes according to histology were calculated before and after 2002. Results: 2384 pts were included. At a 104-mo m-FU, median post-DM FU was 76 mos. Clinicopathologic characteristics were comparable among groups. The use of preoperative chemo (ChT) and radiotherapy (RT) increased from 18% (1987-92) to 29% (2013-17) and from 1.6% to 26%. The rate of preoperative combined ChT-RT also increased from 0.8% to 14.3%. 1st event before SSM was LR in 17.9% pts, DM in 72.2% pts and synchronous LR-DM in 9.3% pts. Table shows 7-yrs outcomes incidence estimates for each period. CCI-SSM (p < 0.001), CCI-LR (p < 0.001) and DMFS (p = 0.040) improved significantly since 2003. 7-yrs postDM survival before vs. after 2003 increased from 15% to 23.6% (p = 0.012). Outcomes by histology were comparable to overall results. Conclusions: In the time frame analyzed, SSM improved by over 15%. An equal improvement in DMFS, the 50% decrease in CCI-LR (1 pts out of 5 had LR as 1st event before death), and the significant postDM increase might explain SSM improvement. Maximum change was seen since 2003 and was paralleled by an increase in the use of preoperative ChT and RT, that might have contributed to a better local and distant control. Of note, the increase in DMFS was not accompanied by a decrease in CCI-DM. The increase in DMFS might be attributable to combined modalities’ ability to offset the negative prognostic impact of positive surgical margins, while no effect was observed on DMs occurred as first event.[Table: see text]
Oncologists' perception of frailty.
Authors: Alam Zuhair , Singeltary Brian Patrick 
Published: June 2021

e24012 Background: Frailty is an under recognized yet clinically important consideration in treatment decision making for older adults with cancer. The Comprehensive Geriatric Assessment (CGA) is considered gold standard for recognition of frailty and is endorsed by the International Society of Geriatric Oncology. Additionally, multiple screening tools have been validated to reliably detect frailty. Nevertheless, studies suggest that formal screening for frailty is not prevalent in community oncology practices and that oncologists’ clinical judgement is not as sensitive in identifying frailty as CGA. This survey was designed to assess the perceptions of frailty amongst oncology providers, as well as the prevalence and method of frailty screening in these practices. Methods: After approval by an independent research ethics board, a secure online survey was circulated amongst community oncology providers within the TriHealth Cancer Institute, including MD’s, DO’s, and NP’s, via email. Survey was live from January 24th to February 12th. Data was analyzed using descriptive statistics. Results: There were 20 total respondents from medical, surgical, gynecologic, and radiation oncology, 70% MD/DO. 70% of total respondents reported having > 50% of their patients over the age of 65. All respondents reported being familiar with the concept of frailty and the ECOG performance status, while only 45% had heard of CGA. 40% respondents reported that they screen for frailty and all used ECOG alone or along with Karnofsky, none used CGA or other validated screening tools. 60% respondents did not formally assess frailty, however all but one felt frailty assessment to be beneficial. Most commonly cited barriers to screening were time restraints and lack of availability of follow up services. Conclusions: Despite proven clinical benefit of CGA and various validated screening tools, few oncology providers screen for frailty. Furthermore, only 45% report having heard of CGA while none incorporate it in their practice. This shows that professional education amongst oncology providers is needed to promote the use of CGA or alternative frailty screening measures to improve outcomes in older adults with cancer. Additionally, strategies must be implemented that would mitigate time restraints and lack of access to follow up services so that these providers may be more inclined to conduct such frailty assessments. Limitations of this study include potential for reporting bias and indeterminate generalizability. Next steps include quality improvement initiative of implementing a frailty screening tool in these practices.
Vaccination coverage in cancer outpatients: An interventional multicenter before/after study.
Authors: Rivière Pierre , Penel Nicolas , Faure Karine , Marie Guillaume , Panaget Sophie 
Published: June 2021

e24026 Background: Despite largely diffused guidelines, Pneumococcal and Influenza vaccination coverage (VC) remains insufficient in cancer patients receiving chemotherapy. We evaluated VC and carried out an interventional study to improve VC in cancer patients treated in 3 medical oncology departments in 3 hospitals of North-of-France. Methods: Using a standardized questionnaire, we assessed the VC in adult cancer patients receiving anticancer treatment in day hospital between 02 and 07 Dec. 2019. Then, in each hospital, we organized trainings with physicians to discuss the current vaccination guidelines (January 2020). Finally, to assess the impact of this intervention on Pneumococcal and Influenza VC, we have conducted a similar survey using the same questionnaire in March 2020. Since there were no specific guidelines on Diphtheria-Tetanus-Pertussis (DTP) VC and we did not expect an improvement, we have monitored DTP VC as internal control. Results: 272 patients have been enrolled in the “before study” in the 3 hospitals, whereas 156 patients have been enrolled in the “after study” in only 2 hospitals (the after-study was not feasible in 3rd hospital because of COVID-19 pandemic national containment). Predictors associated with DTP VC was age, with Pneumococcal VC was center and with Influenza VC were age, gender and tumor histology (adenocarcinoma vs others). Influenza VC was significantly improved after intervention (42.6 vs 55.1% with p = 0.016) especially in fragile patients, but Pneumococcal VC was not (11.8 vs 15.4% with p = 0.357). Conclusions: As expected, VC was very low in cancer patients, our figures are consistent with literature data. The impact of intervention (training of physicians) is limited without improvement of Pneumococcal VC. We presume that this increase in Influenza VC mainly reflects the overall result of national Influenza vaccination campaign.
Does prior treatment with anti-PD 1 immune check point inhibitors (ICIs) mitigate infection with herpes and SARS-CoV-2 viruses: Clinical evidence supporting basic hypotheses.
Authors: Jayarangaiah Apoorva , Gralla Richard J. , McLellan Beth 
Published: June 2021

e24045 Background: We present the initial clinical evidence of likely mitigation of viral infections in patients with non-small cell lung cancer (NSCLC) who previously responded to pembrolizumab. This may constitute a late beneficial effect of ICI treatment, and may identify patients with decreased risk for poor outcomes from major viral infections.While prior clinical reports are lacking, there is abundant laboratory evidence that: 1) immune checkpoint inhibition of the PD-1-mediated signaling pathway augments the response of antigen-specific T cells which likely leads to enhanced viral clearance (Dyke, Eur J Clin Immunol 2017); and 2) high levels of PD-1 positive CD-8 T cells have been demonstrated in HIV, Hepatitis B & C infections, akin to the PD-1 positive tumor-reactive tumor infiltrating cells described in host directed mechanisms against cancer (Rao, Int J Inf Dis 2017). Methods: We report the limited pattern and shortened course of three instances of herpetic infection, and one occurrence of SARS-CoV-2, which suggest enhanced mitigation of viral infection in patients previously treated with ICIs. We have seen no other cases of such limited and rapidly clearing herpes in our thoracic oncology practice. Results: Patient characteristics: ages 38 – 78; 1 female; all stage IV extent; 1 with squamous cell carcinoma and the others had adenocarcinoma/sarcomatoid carcinoma NSCLC; PDL-1 tumor proportion scores > 90% except for the 1 patient with squamous cell carcinoma who had a PDL-1 score < 1%. One patient received only pembrolizumab; the others also received cisplatin-based combination chemotherapy. All responded well to anticancer treatment, were off all treatment for > 1 year, and continue to do well 2 – 5 years after diagnosis. Three infections diagnosed as Herpes zoster presented in each case with only one or two vesicles within a single dermatome. Each infection was diagnosed 48 – 72 hours after eruption, was only minimally symptomatic, and cleared within one or two days. The case of documented SARS-CoV-2 occurred in a 60 year old woman with NSCLC and COPD who was off ICI therapy for 3 years with a complete response. She had minimal COVID-19 symptoms which cleared within 3 days. Conclusions: We conclude that: 1) these cases suggest mitigation of viral infections in patients with NSCLC who had prior anticancer benefit with pembrolizumab, and constitute a long term positive effect of ICIs; 2) these results support the pre-clinical findings and hypotheses of enhanced antiviral immune response with ICI agents; and 3) prospective evaluation of large populations of patients with cancer receiving ICIs is warranted to determine if this benefit is reproducible, what proportion of patients benefit, the magnitude of benefit, and to guide in prospective antiviral treatment in the highly vulnerable NSCLC population.
Feasibility of digital life coaching during stem cell transplantation for multiple myeloma.
Authors: Banerjee Rahul , Huang Chiung-Yu , Dunn Lisa , Knoche Jennifer , Brassil Kelly Jean , Jackson Lindsey , Patel Dhiren , Lo Mimi , Arora Shagun , Wong Sandy Wai Kuan , Wolf Jeffrey Lee , Martin Thomas G. , Dhruva Anand A. , Shah Nina 
Published: June 2021

e24103 Background: Patients with multiple myeloma (MM) experience acute quality of life (QOL) exacerbations following autologous stem cell transplantation (ASCT) that can lead to long-term complications. Life coaching can improve QOL in a structured & personalized manner. We investigated the feasibility of a digital life coaching (DLC) platform, where coaching is accomplished through phone calls and text messages, for patients with MM during ASCT. Methods: Our pilot study (clinicaltrials.gov ID: NCT04432818) enrolled adult patients with MM, English proficiency, and cellphone ownership (smartphone not required). The 16-week DLC program, beginning at Day -5 before ASCT, included unlimited digital access to a certified life coach to help with identifying and accomplishing wellness-related goals. Our primary outcome was ongoing DLC engagement (≥ 1 bidirectional conversation every 4 weeks). Secondary outcomes were ePRO assessments of QOL (PROMIS Global Health), insomnia (PROMIS Sleep Disturbances), and distress (NCCN DT). Electronic patient-reported outcome (ePRO) assessments were delivered via automated REDCap emails every 1-2 weeks. Results: Of 18 screened patients, 15 (83%) enrolled in our study; 2 patients dropped out before initiating DLC (including 1 who was unable to connect with her coach between Day -5 and 0). Of 13 remaining patients, median age was 65 (range 50-81) and 23% had an ECOG performance status of 1 (remainder 0). DLC conversations occurred a mean of every 7.6 days (range 3-28) overall and every 6.5 days (range 2.8-14) during the initial 28-day period including high-dose melphalan and hospitalization. 80% of patients maintained ≥ 1 conversation every 4 weeks. Selected ePRO results (mean ± standard error) are shown in the table. Conclusions: Certain MM patients are able to engage digitally with a life coach and complete email-based ePRO assessments during and after ASCT. Limitations of our study include selection bias and the Day -5 start date, which may be too late logistically and symptom-wise (given our ePRO findings suggestive of peak distress pre-ASCT). DLC may play an innovative and scalable role given the emphasis on remotely delivered care during the COVID-19 pandemic. A Phase II randomized study of DLC versus usual care is under way (clinicaltrials.gov ID: NCT04589286). Clinical trial information: NCT04432818. [Table: see text]