bluuebunny/crossref_metadata_2025_split huggingface dataset:
The feasibility and potential role of pharmacogenetics to improve drug safety in patients with advanced cancers.
Authors: Darabi Sourat , Weatherill Chelsey , Dalili-Shoaie Valentina , Eisenberg Burton Larry , Demeure Michael J. 
Published: June 2021

e22522 Background: Pharmacogenetics is the study of genetic variants that define drug metabolism and dosing requirements, response or toxicity. Knowledge regarding drug-drug interactions and individual variations in genes involved in drug metabolism is increasing. Since patients with cancer often take several drugs (polypharmacy), they have a higher risk of severe drug interactions. The FDA lists several pharmacogenetic biomarkers in drug labeling, including genetic variants that impact how certain medications are prescribed. The drugs listed span multiple medical applications, including but not limited to oncology, primary care, psychiatry, neurology, cardiology, and many more. Adverse drug reactions are a significant cause of morbidity and mortality, yet the use of pharmacogenetic testing has not yet become established as a routine in clinical practice. Herein we sought to study the feasibility of applied pharmacogenetics in a pilot drug safety program in patients with advanced cancer. Methods: We enrolled patients in a prospective single-center IRB approved study. Patients with advanced cancer on three or more drugs about to begin chemotherapy at the Hoag Family Cancer Institute were eligible. Informed consent was obtained from the study participants, and their samples were sent to a CLIA laboratory to conduct a 25-gene pharmacogenetics testing panel, which includes “major drug-metabolizing enzymes” CYP2D6, CYP2C19, CYP2C9, CYP3A4, and CYP3A5 as well as other genes with known drug implications. We recorded patients’ demographics and clinical information. In addition, participant’s drug lists were assessed for potential polypharmacy interactions. Results: We analyzed the results from 36 patients, 20 females and 16 males, enrolled between December 2017 and June 2020. Pharmacogenetics results from these patients showed that 61% (22 patients) had a variant with gene drug interaction indication. The most common variants were identified in the CYP2D6 gene, followed by CYP2C19, CYP3A4, and CYP3A5. Of these 22 patients, seven patients had at least one major criterion (drug interactions may lead to severe clinical effects), and eight patients with reported moderate criteria (may lead to substantial clinical effects). Additionally, seven patients had variants with both major and moderate criteria. Patients were taking an average of 10 medications per person ranging from 3-19 drugs. No patient, however, experienced significant drug toxicity during the observation interval. Conclusions: Patients with advanced cancer are at particular risk for polypharmacy and adverse drug reactions. Our data report supports pharmacogenetics testing as being feasible for oncology patients. Therefore, programs to prevent or limit the frequency and severity of drug reactions warrant further exploration as they offer the potential to improve patient safety and decrease healthcare costs.
Challenges in lung cancer multidisciplinary collaboration experienced by specialists in four countries.
Authors: Murray Suzanne , Subbiah Vivek , Grohé Christian , Nakagawa Kazuhiko , Zahabi Sacha , Sireci Anthony , Sherman Steven I. , Kelly Elizabeth , Lazure Patrice 
Published: June 2021

e23002 Background: The importance and challenges of Multidisciplinary Team (MDT) collaboration in managing lung cancer have been increasingly recognized in an ever more complex therapeutic environment. Data on physicians’ viewpoints regarding MDT collaboration in lung cancer care, collected in a broader study assessing challenges related to lung/thyroid cancer patient management, are presented. Methods: A mixed-methods approach was used to analyze this data, combining qualitative interviews and a quantitative survey. Pulmonologists (PLM), oncologists (ONC) and pathologists (PTH) from Germany (GE), Japan (JP), the United Kingdom (UK) and the United States (US) were recruited. Results: A total of 44 specialists participated in interviews and 377 in a survey. Quantitative data reveal that 53% of pulmonologists in JP and 39% in GE have suboptimal knowledge of the timing of patient referral to an oncologist. Fewer PLM/PTH from JP (43%/47%) report a fully integrated MDT team approach in their clinical setting, compared to those from GE (80%/95%), the UK (96%/82%) and the US (82%/97%). Qualitative data indicate that current MDT team practices are perceived as delaying patient care due to significant inefficiencies (sometimes due to lack of knowledge/skills) and unclear responsibilities within the team. Around half of ONC in each country and 78% of PLM from the UK report a gap in knowledge and relevance of each genetic biomarker test according to clinical presentation. PTH in the UK (70%), the US (50%), and JP (72%) report sub-optimal skills identifying biomarker tests to inform the progression of lung cancer (also a challenge for PLM/ONC). Conclusions: This study indicates a need for multi-level interventions addressing systemic and attitudinal barriers as well as knowledge gaps which affect physicians’ ability to collaborate in lung cancer care.
Fostering interspeciality learning in cancer survivorship care: Learning suite results.
Authors: Chaput Genevieve , Sussman Jonathan , Williams Tristan 
Published: June 2021

e23003 Background: As survivorship provision declines within cancer centres, primary care providers are increasingly entrusted in the follow-up care of cancer survivors. Empowering specialists and primary care providers about survivorship through educational interventions is essential. Interspecialty education is poorly integrated into residency training, which may impede collaboration between different providers in practice. Interspecialty partnership can positively impact patient and resource-use outcomes. The aim of this study was to assess if a cancer survivorship learning suite (LS) impacts attitudes of family medicine, radiation oncology and medical oncology trainees towards interspecialty collaboration in Montreal, Canada. Methods: A survivorship (LS) developed by a Manitoba-based team under the sponsorship of a Canadian Partnership Against Cancer grant held by Cancer Care Ontario was delivered to 49 McGill University family medicine, radiation oncology, and medical oncology trainees. The LS comprised in-person delivery of a 3-hour case-based workshop, presented by a radiation oncologist and a family physician, both experienced in the field of survivorship. An adapted version of the Readiness for Interprofessional Learning Scale (RIPLS) was completed by participants before and after workshop delivery. Statistical analyses included non-parametric (Wilcoxon Signed rank tests) comparisons. Results: Response rate was 63.2%, and included family medicine (65%), radiation oncology (26%), and medical oncology (10%) trainees, respectively. Following the workshop, participants were significantly more likely to agree that interspecialty learning in residency “would help physicians become better team workers”, (Z = 2.7, p < 0.008, n = 31), and “improves relationships between physicians of different specialties in independent practice afterwards”, (Z = 2.6, p < 0.009, n = 31). Participants were also significantly more likely to agree that “shared interspecialty learning < would > increase < their > ability to understand clinical problems”, (Z = 2.8, p < 0.005, n = 31). Conclusions: While much literature has focused on interprofessional collaboration at different levels of education and practice, few studies have assessed interspecialty collaboration of physicians of different specialties. This survivorship LS demonstrated favorable changes in attitudes towards interspecialty learning.
Apatinib plus ifosfamide and etoposide (IE) versus IE chemotherapy alone for relapsed or refractory osteosarcoma.
Authors: Xie Lu , Guo Wei , Xu Jie , Gu Jin , Tang Xiaodong , Li Yuan , Sun Kunkun 
Published: June 2021

e23502 Background: Results of previous study showed promising objective response but short-lived activity of apatinib in the treatment of osteosarcoma refractory to first-line chemotherapy, from which we observed the disease control of musculoskeletal lesions were worse than pulmonary lesions. This treatment failure has partly been overcome by the addition of Ifosfamide and etoposide in OLIE study. We aimed to retrospectively compare the activity of apatinib in combination with IE in relapsed or refractory osteosarcoma with synchronous patients receiving IE chemotherapy alone in two sarcoma centers in China. Methods: We retrospectively analyzed medical files and radiographic materials of patients with osteosarcoma relapsed or refractory to first-line chemotherapy, who had received combination of apatinib and IE regimen or IE chemotherapy alone between June 3rd, 2017 and July 17th, 2020. Seventy-nine patients were included, of whom 33 patients received apatinib in combination with IE and 46 patients received single IE chemotherapy. Results: Patients’ tumor burden and general status were obviously different between these two groups with 16/33 (48.5%) patients receiving apatinib+IE having both Lung and musculoskeletal lesions at baseline and 39/46 (84.8%) patients receiving single IE having just pulmonary lesions at baseline. However at last follow up 16/33 (48.5%) of patients receiving apatinib+IE had all lesions resected while 23/46 (50.0%) of patients receiving IE alone had their lesions resected, which might partly due to down-staging of the diseases. With median follow-up time of 28.4 (IQR, 16.1-38.3) months, 21/33 (63.6%) patients receiving apatinib+IE had objective responses while 13/46 (28.3%) patients receiving single IE chemotherapy had responses. The median event-free survivals (EFS) were respectively 11.4 (IQR, 6.7-18.4) months for apatinib+IE and 11.2 (IQR, 4.4-21.8) months for IE alone without significant statistical differences (P = 0.47). The overall survival (OS) was obviously different because of disease stage and tumor burden according to Kaplan-Meier analysis with median OS time of 30.4 (IQR, 21.8-not reached) months for IE alone and 19.8 (IQR, 13.1-30.6) months (P = 0.019). Conclusions: For osteosarcoma with multiple sites’ metastasis, apatinib plus IE demonstrated clinically meaningful antitumor activity in patients with recurrent or refractory osteosarcoma after failure of MAP/I chemotherapy or even single apatinib or IE treatment alone, with a positive effect on delaying disease progression. This combination deserves further investigation in prospective trials with manageable toxicity.
Efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic Ewing sarcoma.
Authors: Dogan Izzet , Iribas Ayca , Ekenel Meltem , Basaran Mert 
Published: June 2021

e23510 Background: The purpose of the study was to evaluate the efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in heavily pretreated adult patients with metastatic Ewing sarcoma. Methods: We evaluated data of the patients with metastatic Ewing sarcoma retrospectively. We recorded clinical, pathological, radiological, and treatment features of the patients and used SPSS 25. version for statistical analysis. Kaplan-Meier and Cox regression analysis were used for survival analysis. Results: Sixteen patients were included in the study. The median age was 25 (range, 20-42) years. Eleven (68.8%) of the patients were male. The origin of the tumor was bone (75%) and soft tissue (25%). The most common primary tumor localization was pelvic (41.7%), extremity (33.3%), and other sites (25%), respectively. Six (37.5%) patients were de-novo metastatic at diagnosis. The most common metastatic site was the lung (75%). Before the vincristine, irinotecan, and temozolomide (VIT) combination, patients had received at least two different chemotherapy regimens (87.5%) and palliative radiotherapy (37.5%). Median progression-free survival was 3.4 (95% CI, 1.8-4.9) months. The partial response was observed in five (31.3%) patients, and all other patients (68.7%) had progressive disease. Grade 1-2 adverse events were observed in thirteen (81.3%) patients and grade 3-4 in five (31.3%) patients. The most common adverse events were hematological (87.5%). Median overall survival was 5.6 (95% CI, 3.6-7.5) months. Conclusions: In this study, we showed real-life efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic osteosarcoma. Toxicities were concern about in these heavily pretreated patients. Treatment options of metastatic Ewing sarcoma are limited. VIT regimen may be considered in patients who have a good performance.
Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.
Authors: Tararykova Anastasia Alekseevna , Bokhyan Beniamin , Konev Andrey A. , Falkina Polina A. , Kumekhov Zaur Yu. , Valiev Aslan K. 
Published: June 2021

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.
Health-related quality of life after isolated limb perfusion compared to extended resection, or amputation for locally advanced extremity sarcoma: Is a limb salvage strategy worth the effort?
Authors: Reijers Sophie J.M. , Husson Olga , Soomers Vicky L.M.N. , Been Lukas B. , Bonenkamp Han J. , van de Sande Michiel A.J. , Verhoef Cornelis , Van Der Graaf Winette T.A. , van Houdt Winan J. 
Published: June 2021

e23539 Background: Induction isolated limb perfusion (ILP) followed by limb-sparing resection or extended resection are frequently used limb salvation strategies (LSS) in locally advanced extremity soft tissue sarcoma (eSTS) to prevent amputation. However little is known about the long term health-related quality of life (HRQoL) in these patients. The aim of this study was to compare long-term patient reported outcomes (PROs) such as HRQoL after ILP compared to extended resection or amputation. Methods: Patients treated with an ILP, extended resection, or amputation were selected from the respondents of a multi-institutional cross-sectional cohort survivorship study (SURVSARC) conducted 2-10 years after diagnosis among sarcoma survivors registered in the Netherlands Cancer Registry (NCR). Extended resection was defined as resection for stage III eSTS, details regarding amputation levels other than upper or lower extremity are unknown. Used PROs were the EORTC QLQ-C30, Cancer worry scale (CWS), the Hospital Anxiety and Depression Scale (HADS), and the Toronto Extremity Salvage Score (TESS). Results: We identified 96 eSTS survivors and assigned them into four groups: ILP (N = 20), extended resection (N = 48), primary amputation (N = 20), and amputation after ILP (N = 8). While there were no differences in PROs between ILP and extended resections, results showed better functioning and functionality after these two LSS groups versus the amputation groups. The amputation groups scored significantly lower on the EORTC QLQ-C30 physical functioning scale (p < 0.001, 62.7 and 65.7 versus 78.0 and 84.1) and role functioning scale (p = 0.038, 67.5 and 52.8 versus 79.2 and 80.9), which both account for a difference with ‘medium’ clinical relevance. Also for the TESS, the scores were significantly lower for the amputation groups compared to the LSS groups (upper extremity p = 0.007 with 68.9 and 71.6 versus 93.3 and 91.1; lower extremity p < 0.001 with 72.2 and 50.9 versus 84.5 and 85.5). There were no significant differences on cancer worry, anxiety and depression were found between all groups. Conclusions: Based on this survivorship study, HRQoL in eSTS survivors treated with ILP followed by limb-sparing resection is not inferior to extended resections, however it is superior in maintenance of physical functioning and functionality compared to an amputation.[Table: see text]
A retrospective study to evaluate the safety and efficacy of anlotinib plus camrelizumab in management of advanced retroperitoneal sarcoma.
Authors: WU Jianhui , Qiu Hui , Lv Ang , Liu Bonan , Liu Qiao , Li Chengpeng , LIU Daoning , Wang Zhen , Tian Xiuyun , Hao Chunyi 
Published: June 2021

e23545 Background: Several studies have demonstrated the antitumor activity of single-agent anlotinib in the treatment of soft tissue sarcoma (STS). However, the most effective results were from cases of alveolar soft part sarcoma (ASPS), which was a rare subtype in retroperitoneal sarcoma (RPS). The therapy of RPS is still dismal. Thus, we evaluated the effectiveness and safety of anlotinib plus camrelizumab for the treatment of RPS. Methods: We retrospectively reviewed the data of 36 patients with advanced/metastatic RPS in Sarcoma Centre of Peking University Cancer Hospital from July 2019 to February 2021. Anlotinib was given 12mg Qd 2 weeks on and 1 week off, and camrelizumab was transfused 200mg at Q3w. Patients that underwent at least 4 cycles of therapy were enrolled in this study. The primary endpoint is objective response rate (ORR) and evaluated according to the irRECIST 1.1 criteria. Results: The pathologic subtypes of enrolled cases include liposarcoma (LP) (n = 16), leiomyosarcoma (LMP) (n = 5), uncertain differentiation sarcoma (n = 7), fibroblastic and myofibroblastic tumours (n = 4), rhabdomyosarcoma (n = 2) and malignant peripheral nerve sheath tumour (MPNST) (n = 2). Two patients (5.6%) achieved CR and 9 patients (25.0%) achieved PR, with an ORR of 30.6%. Eighteen patients (50.0%) achieved SD and 7 patients (19.4%) were evaluated as PD, with the disease control rate (DCR) of 80.6%. The progression-free rate (PFR) at six months was 60.0%. Five patients underwent further radical surgical resection. The two CR cases were diagnosed as dedifferentiated liposarcoma (DDLP) and MDM2 amplified MPNST respectively, and both patients have been under CR status for over 12 months until now. The only grade 3 or higher treatment related adverse event was hypertension (22.2%). Camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) was not observed in this group of patients. Conclusions: The combination of anlotinib and camrelizumab demonstrated encouraging efficacy and safety in the treatment of RPS. A further clinical study with biomarker exploration should be performed in the future.
Activity of single-agent gemcitabine in patients (pts) with advanced angiosarcoma: A retrospective study.
Authors: Watson Sarah , Verret Benjamin , Ropert Stanislas , Adam Julien , Bahleda Rastilav , Briand Sylvain , Cavalcanti Andrea , Chamseddine Ali N. , Court Charles , Fadel Elie , Faron Matthieu , Haddag Leila , Henon Clemence , Le Pechoux Cecile , Levy Antonin , Mercier Olaf , Ngo Carine , Honoré Charles , Le Cesne Axel , Mir Olivier 
Published: June 2021

e23547 Background: Gemcitabine has shown clinical activity against angiosarcoma in single cases or small series, as a single agent or in combination with taxanes. We aimed to evaluate its activity in a larger, homogeneous series of pts with advanced angiosarcoma. Methods: We retrospectively reviewed the electronic medical records of consecutive adult pts with advanced angiosarcoma treated with gemcitabine(1000 mg/m2 IV days 1, 8 and 15 of a 28-days cycle) at our institutions from January 2010 to January 2021. All cases were confirmed by an expert pathologist from the French network of Sarcoma pathologists (RRePS). Response was evaluated according to RECIST 1.1, and survival was estimated using the Kaplan-Meier method. Results: Fourty-two pts [median age : 52 years (range : 25-90), median PS : 1 (range : 0-2), 36 women)] were identified. Ten (24%) had locally advanced disease; the median number of metastatic sites was 2 (range : 1-4) in the remaining 32 pts. Primary tumor site was breast/chest wall (12), face/scalp (9), heart (8), other viscera (7) or limbs (7). Eleven (26%) occurred in previously irradiated field. All pts but 4 had received prior anthracyclines (peri-operatively or in the metastatic setting) and weekly paclitaxel, and 9 (21%) had received pazopanib. Gemcitabine was given as second, third and fourth line in 7 (17%), 20 (47%) and 15 (36%) pts, respectively. Best tumor response by RECIST 1.1 was PR (16 pts, 38%), SD (10 pts, 24%) or PD (16 pts, 38%). All pts with cardiac angiosarcoma experienced a PR, as well as 4 of 10 pts with angiosarcoma arising in irradiated field and 3 of the 4 pts with CNS metastases. Median PFS was 5.4 months (95%CI : 3.1-6.5), and median OS was 9.9 months (95%CI : 6.6-13.4). Two febrile neutropenia occurred. No new safety signal was observed. Ongoing studies are exploring whether candidate biomarkers such as hENT1 expression could help predicting the benefit of gemcitabine in pts with angiosarcoma of the heart and large vessels. Conclusions: Single agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma (including cardiac angiosarcoma). This series may serve as a benchmark for future clinical trials in angiosarcoma.