bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collaborating with low- and middle-income countries: Experience from two of the United Kingdom’s comprehensive cancer centers.
Authors: Foreman Emma , Leslie Isla , Lyons Hannah , Piddock Katherine , Sadanandam Anguraj , Sanneh Alison , Stanway Susannah Jane , Webb Julie , Cowan Richard 
Published: June 2021

e23014 Background: The number of annual global cancer deaths is rising and the majority of this burden, for a multitude of reasons, falls in low- and middle- income countries (LMICs). With the United Nations’ 3rd and 17th Sustainable Development Goals in mind (which include by 2030 “reduce by one third premature mortality from non-communicable diseases” and “partnership for the goals”) a survey was undertaken at the UK’s two largest comprehensive cancer centres to scope individual and team endeavours to work with colleagues in less well-resourced countries. Methods: Employees at the Royal Marsden Foundation Trust (RM) and Institute of Cancer Research (ICR) in London and Surrey, UK and The Christie NHS Foundation Trust (Christie), Manchester were invited to complete a survey to capture collaborative clinical care, research, education and training. Results: Responses were received from 520 multidisciplinary individuals across the 2 centres to two similar questionnaires. A large number had experience of working in some capacity in, or in collaboration with an LMIC. At the RM 14.62% of respondees were currently working with colleagues in LMICs. At The Christie 13.22% of staff had experience of working in LMICs in a supportive capacity. Those currently collaborating with colleagues in LMICs were working in a wide range of countries across Asia, Africa and South America in a range of initiatives spanning clinical care, research, education and training. Of those who answered the survey 64% at The Christie said they’d like to hear more about opportunities to be involved in supporting global health care, and 89% at RM/ICR said they’d be interested in joining a collaborative group working on global oncology initiatives at the institutions. Conclusions: This survey highlights the body of willing, interested individuals keen to work with colleagues in LMICs to improve cancer outcomes. The launch of the UK Global Cancer Network in 2020 will build upon these two surveys with a planned national survey of global health and cancer work undertaken by individuals in 2021.
Efficacy and safety of anlotinib hydrochloride in the treatment of advanced bone and soft tissue sarcoma after failure of first-line chemotherapy.
Authors: Yao Weitao , Wang Jiaqiang , Zhang Peng , Wang Xin , Yan Qiang , Du Xinhui , Tian Zhichao , Niu Xiaoying 
Published: June 2021

e23504 Background: There were limit treatments for bone and soft tissue sarcomas that have failed chemotherapy. Anlotinib hydrochloride is a multi-targeted receptor of tyrosine kinase inhibitors (TKI), which has shown therapeutic effects on soft tissue sarcoma. Methods: This is a single-arm, prospective, single-center clinical study. The included criteria were patients with pathological diagnose of bone and soft tissue sarcoma, at least one measurable lesion (criteria of RECIST 1.1), failed of more than one line therapy (except for sarcoma subtypes insensitive to chemotherapy), with the normal function of main organs. All patients received 12mg of anlotinib once daily, 2 weeks on and 1 week off until progression or unacceptable toxicity. The primary endpoint was ORR. We also observed PFS, OS, DCR and AEs. Results: From October 2018to October 2020, a total of 40 patients were enrolled. 25 were men and the median age of the patients was 43.28 (8-79) years. The tumor was located on the trunk in 14 cases, on the limbs in 24 cases and on the abdominal wall in 2 cases. 77.5%, 10%, 7.5% and 5% of patients have lung metastases, bone metastasis, liver metastasis and lymph node metastasis, respectively. The main subtypes included synovial sarcoma (20%), alveolar soft tissue sarcoma (15%), osteosarcoma (12.5%), fibrosarcoma (10%), undifferentiated pleomorphic sarcoma (7.5%). 32.5% of patients had received for at least second-line prior therapy and 25% of patients had received apatinib as a previous treatment. The ORR was 15% and the DCR was 77.5%. Patients who had received apatinib had an ORR of 10% and a DCR of 80% in this group. mPFS were 7.0 months (95%CI = 5.07-8.93) and 7.13 months (95%CI = 5.28-8.98) in overall patients and patients who had received apatinib respectively. The mPFS of ASPS, synovial sarcoma, fibrosarcoma, and osteosarcoma were 17.0 months, 8.2 months, 7.1 months, 2.9 months (p = 0.017). The mOS has not been reached. Adverse events were mainly in grades I and II, The ≥3 AEs were hypertension (2.5%), proteinuria (2.5%), leukopenia (2.5%), thrombocytopenia (2.5%), anorexia (2.5%) and elevated transaminase (5.0%). Conclusions: Anlotinib is effective and safe in the treatment of bone and soft tissue sarcoma, and its efficacy is positively correlated with special types (such as ASPS, synovial sarcoma), effectiveness can also be observed in patients who have failed in other targeted therapy. Clinical trial information: NCT04223583.
Metastatic osteosarcoma at diagnosis: Analysis of 92 cases from a single institution.
Authors: Longhi Alessandra , Broll Valquiria , Righi Alberto , Carella Antonio , Pierini Michela , Ferrari Cristina , Cesari Marilena , Hakim Rossella , Paioli Anna , Palmerini Emanuela 
Published: June 2021

e23506 Background: Metastatic osteosarcoma (MOS) with synchronous metastases accounts for 20-25% of all new cases of osteosarcoma. Lungs are the most common site of metastases at presentation (80%) followed by Bone (10%). 5- years Overall Survival (OS) of MOS ranges from 11 to 40%. In a previous study from our institution (Bacci G 2006) on 57 pts < 40 years old (1995-2000) the 2- and 5-year OS were 55% and 18%. Methods: Data of patients with pathologic and radiologic confirmed MOS with adequate follow up were reviewed (EC Approval N 916/2020/Oss/IOR). Time-to-event outcomes were estimate with Kaplan-Meier method and compared between groups with log-rank test and Cox model. Results: From August 2000 to October 2018, 92 patients had a diagnosis of MOS: median age 16.5 yrs (6-73, twelve pts > 40 ), gender rate was M 51/F 41, axial primary tumor in 15 cases, extremity in 77. Lung only metastases were described in 66 (71.7%). In 75/90 cases primary tumor was surgically removed, 43 (46%) cases had at least one surgical metastasectomy. All patients received chemotherapy: preoperative only in 6 cases, postoperative in 6, and pre and postoperative in 66 patients. The 1st line chemotherapy was a combination of drugs: Adriamycin in 91/92 pts, Cisplatin in 89/92, Ifosfamide in 88/92, Methotrexate in 83/92; 59 patients received a 2nd line chemotherapy, 34 pts received a 3rd line; most employed regimen were Gemcitabine-Docetaxel, Ifosfamide 15 gr/m2, Cyclophosphamyde-Etoposide, TKI (Pazopanib, Sorafenib), and a few received experimental drugs. Complete remission (CR) was obtained in 26/92 (28%), in 19 cases after surgical metastasectomy.In 30 pts the information of PGP (P- glycoprotein) was available; patients with positive PGP (19/30) had a worst overall survival as compared to those PGP negative (P = 0.038). Of those in Complete Remission 14/26 relapsed. At December 2020 with a median follow-up of 95 ms (IQR 34-159): 65/92 (70%) died , 12 are alive and free from disease , 6 are alive with disease, 9 were lost . The 2-yrs OS for all 92 pts from diagnosis was 66% (95%CI 55-75) and 5-yrs OS was 26% (95% CI 16-37). From the end of treatment, for those who reached a CR the 5-year OS was 57% vs 9% for those who did not (P < 0.001). At univariate analysis, primary tumor site (2-y OS 48% axial vs 72% extremity, P < 0.001), site of metastases (2-y OS 74% only lung vs 48% other, P = 0.004) and number of lung nodules (P = 0.007), were significantly associated to OS. At multivariate analysis, only site of metastases (other vs. only lung HR = 2.26, 95%CI: 1.21-4.22) and number of lung nodules (≥10 nodules vs ≤3 HR = 2.44, 95%CI: 1.24-4.81) were confirmed as significant for OS. Conclusions: Compared to our previous report from 20 yrs ago, 2-years and 5 yrs OS of MOS has improved but it remain unsatisfactory (66% vs 55% and 26% vs 18%).
Clinicopathological features and treatment of perivascular epithelioid cell tumor.
Authors: Lin Ying , Liu Xin , Zhang Xiaowei , Chen Yong , Wang Chunmeng , Wang Shengping , WANG Jian , Luo Zhiguo 
Published: June 2021

e23538 Background: Perivascular epithelioid cell tumor (PEComa) is a rare form of mesenchymal neoplasms. No clinical trial of large sample size regarding medical treatment of PEComa has been reported so far. Previous retrospective studies with small sample size have showed efficacy of mTOR inhibitors as treatment of PEComa. This study aimed to analyze the clinicopathological features of PEComa, and the efficacy of mTOR inhibitor in advanced PEComa. Methods: Medical information of patients diagnosed with PEComa and treated in Fudan University Shanghai Cancer Center were collected. Survival analysis was performed by Kaplan-Meier method. Radiological response was assessed according to RECIST version1.1. Results: A total of 17 patients were treated in our center during June 2007 to June 2020. PEComa mostly occurs in middle-aged women. The most common primary sites are pelvis, lung and abdomen. Relapse usually occurs within 2 years after radical surgery. Radical surgery is the main treatment for PEComa of limited stage, and remains the main option for those with limited recurrent lesions. Of the 13 patients with advanced malignant PEComa in our cohorts, the objective response rate of mTOR inhibitors in advanced malignant PEComa was 45.5%, and median progression-free survival was 27.7 months (95% CI 4.7-50.5 months). 2 patients discontinued mTOR inhibitor treatment due to pneumonitis combined with dyspnea and fever respectively. Conclusions: For advanced malignant PEComa, mTOR inhibitors are effective. Lung toxicity of mTOR inhibitor should be monitored.
Loss of 5'ALK leads to better response to crizotinib in sarcomas with ALK rearrangement.
Authors: Li Bin , Hu Yongbin , He Qiongzhi , Lu Jingchen , Huang Gengwen , Xiao Sheng 
Published: June 2021

e23554 Background: Crizotinib targets abnormal ALK activation, however, the clinical responses vary among patients with ALK rearrangement. A recent study showed that the NSCLC patients with 5'ALK loss have a favorable response to Crizotinib with doubled progression-free survival (PFS). We asked whether sarcoma patients with ALK rearrangement have a similar correlation between 5'ALK loss and clinical response to Crizotinib. Methods: The histopathologic diagnosis was made on H&E staining and IHC, including anti-ALK(D5F3). DNA isolated from FFPE materials was subjected to an NGS assay targeting 295 genes including ALK rearrangement. Results: 4 cases were detailed in Table. Case#1 is an inflammatory myofibroblastic tumor with a PLEKHH2-ALK rearrangement, which was previously reported in an NSCLC but not in sarcomas. Case #2 is an undifferentiated sarcoma with 2 ALK fusions, RANBP2-ALK and TMEM217-ALK, both in-frame fusions containing intact tyrosine kinase domains. The TMEM217-ALK is a novel fusion. Case#3 is a leiomyosarcoma with MYH9-ALK fusion, which was often seen in ALK-positive large B-cell lymphoma but not in sarcoma. Case #4 is an undifferentiated sarcoma with EML4-ALK fusion. All 4 cases had positive ALK IHC, consistent with the expression of ALK fusion proteins. Case#1 and #2 had a loss of 5' ALK, while case #3 and #4 retained the 5' ALK. All cases received and responded to Crizotinib therapy, with the Karnofsky Performance Status (KPS) improved from 30-60 score pre-therapy to 90-100 score after 3 months of Crizotinib. While Case#3 and #4, both retained the 5' ALK, relapsed at 9.4 m and 6.1 m, case#1 and #2, both lost 5' ALK, remain progression-free at 15m and 27m, respectively. The side effect was manageable with a grade II hepatic toxicity in only one patient. Conclusions: We report here 4 sarcomas with ALK rearrangement, including a novel fusion TMEM217-ALK. Two of these cases had a 5' ALK loss in addition to the 3' ALK rearrangement, and both had much longer PFS on Crizotinib therapy. The underlying mechanism deserved further investigation. Four fibrosarcomas with ALK rearrangements and their response to Crizotinib therapy.[Table: see text]
Feasibility of a telemedicine lifestyle-based rehabilitation program (HEAL) for gynecologic cancer patients.
Authors: McKenzie Nathalie Dauphin , Gwacham Nnamdi Ifekandu , Pepe Julie W. , Ahmad Sarfraz , Kendrick James Erasmus , Holloway Robert W. 
Published: June 2021

e24033 Background: General health related factors such as obesity, unhealthy diets disproportionate with sugary and highly processed foods, inactivity, and smoking have repeatedly been shown to negatively impact survival and quality of life outcomes in cancer survivors. The Healthy Eating Active Lifestyle (HEAL) – GYN “rehabilitation” cancer program was developed to provide intensive group lifestyle training on exercise, nutrition, sleep, social integration, and stress management via a telemedicine platform. The aim of this study was to determine the feasibility of such an intervention and its tolerability, in addition to its impact on short-term quality of life for gynecologic cancer patients. Methods: HEAL – GYN consists of 8 weekly group sessions offering experiential instruction and personalized goal setting for patients with diagnosis of gynecologic cancer. Components are drawn from the tenets of lifestyle medicine. An oncologist certified in lifestyle medicine along with a multidisciplinary rehabilitation team addressed diet, physical activity, strategies for sleep and stress management, smoking cessation, and alcohol intake. The intervention included training to address unmet psychologic, emotional, physical, sexual, social, and spiritual needs common to cancer survivors. American College of Lifestyle Medicine questionnaires were administered, utilizing Likert scales (1-5) in a pre- and post- fashion to assess improvements in physical activity levels, dietary habits, sleep hygiene, and quality of life. Medical records were reviewed including anthropometric data. Results: 26 patients have enrolled thus far, and we report outcomes on the first 20 participants. The mean age was 58.8 years; 22 were Caucasian, and 7 were on maintenance therapies for gynecologic cancers. Average total severity of reported symptoms (scale = 100 points) on a general medical symptom questionnaire (MSQ) decreased by 22% (61 vs 48). Eight patients reported increased perceived levels of health and 6 had stable perception of health. There were also notable improvements from baseline in item assessments of eating behavior (34%), perceived stress (20%), and resilience (21%). Patients also reported a notable trend towards improvement in anxiety (35%) and depression (34%), as well as social integration and connectedness (30%). 100% of participants would “highly recommend the program” and none complained of stress or altered mood associated with online instruction. Conclusions: The telemedicine HEAL – GYN peri-habilitation program is feasible and well tolerated. In addition, the program may improve quality of life and may prevent further decline for those on treatment or maintenance therapy. These preliminary findings support continued investigation of a telemedicine healthy lifestyle peri-habilitative program.
Predictors of venous thromboembolism in cancer patients using machine learning.
Authors: Cali Daylan Ayse Ece , Khemasuwan Danai , Kim Hyun S. , Geetha Parvathy , Alarcon Velasco Sylvia Vania , Lathan Christopher S. 
Published: June 2021

e24042 Background: The increased risk of venous thromboembolism (VTE) in cancer patients is clearly documented. However, given the heterogeneity and increased risk of bleeding in cancer population, patient selection for thromboprophylaxis is still challenging. Methods: In order to predict risk factors of VTE in cancer patients, we performed a retrospective study of 706 patients who were diagnosed with either solid or hematological malignancies between 2015 and 2019. Demographics, body mass index, complete blood count with differential, kidney function tests, electrolytes, liver function tests, lipid profile and cancer staging were recorded. Random forest analysis with bagging was used to rank these variables and the Kaplan-Meier survival analysis was implemented to stratify cancer subtypes based on the risk of VTE occurrence. Results: The mean follow-up time was 19 months. 8.2% of the patients developed VTE. Based on the random forest analysis, the most important five factors in prediction of VTE in cancer patients were determined as cancer subtype, white blood cell count, platelets, neutrophil and hemoglobin. At one-year mark, the risk of VTE in lung cancer and hematological malignancies was found to be significantly higher than breast, colorectal and endometrial cancer (p<0.05). Conclusions: Machine learning approach is infrequently used in risk factor prediction of VTE in cancer patients. The risk factors identified by the machine learning algorithm in our study are consistent with prior studies and show a clear difference in risk of VTE in various cancer subtypes. Moreover, hematological malignancies and lung cancer patients may develop VTE earlier than other cancer subtypes based on the Kaplan-Meier analysis. Further prospective studies with longer follow up are needed to better risk-stratify cancer patients and explore the temporal associations of VTE risk factors. [Table: see text]
Association of OPRM1, MIR23B, and MIR107 genetic variability with acute and chronic pain after postoperative tramadol treatment in breast cancer.
Authors: Besic Nikola , Goricar Katja , Vidic Zala , Strazisar Branka , Dolzan Vita 
Published: June 2021

e24052 Background: Tramadol is an opioid analgesic often used for pain management after axillary lymph node dissection in breast cancer. It exerts its analgesic activity through activation of the G protein-coupled µ-opioid receptor, encoded by the OPRM1 gene. Genetic factors that may modify activity or expression of OPRM1 could thus affect the efficacy of tramadol treatment. This study investigated the association of genetic variability of OPRM1 and genes coding for miRNAs regulating OPRM1 expression with pain management in breast cancer patients treated with tramadol after surgery. Methods: The study included 113 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after breast cancer surgery within the randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for OPRM1 rs1799971 and rs677830, MIR23B rs1011784 and MIR107 rs2296616 using competitive allele-specific PCR. The association of genetic factors with acute and chronic pain was evaluated using logistic regression, Fisher’s exact test and Mann-Whitney test. Results: The investigated OPRM1 related genetic factors were not associated with acute pain measured using VAS scale within four weeks after surgery, even after adjustment for tramadol dose (all P > 0.05). One year after surgery, 21 (21.1%) patients experienced chronic pain and 25 (25.3%) experienced neuropathic pain. In carriers of two polymorphic MIR107 rs2296616 alleles, chronic pain was significantly more common compared to carriers of two wild-type alleles (35.3% compared to 0% of patients, P = 0.004). Carriers of at least one polymorphic MIR23B rs1011784 allele experienced more neuropathic pain compared to carriers of two wild-type alleles after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07-7.59, P = 0.036). Conclusions: Genetic variability of miRNAs that could affect OPRM1 expression may be associated with chronic pain in breast cancer patients treated with postoperative tramadol.
Pre-anthracycline left ventricular ejection fraction (LVEF) assessment and long-term cardiovascular (CV) outcomes in adolescent and young adult (AYA) lymphoma survivors.
Authors: Farooque Alma , Carroll Cibele , Tevaarwerk Amye Juliet , Pophali Priyanka Avinash 
Published: June 2021

e24060 Background: Anthracyclines are known to cause long-term cardiotoxicity. There are no specific guidelines for CV screening and follow-up of AYA patients treated with anthracyclines. Pediatric guidelines focus on long-term imaging surveillance, while for adults, LVEF assessment prior to anthracyclines is recommended. Multiple studies have demonstrated LVEF assessment rarely impacts treatment decisions, especially in the absence of CV symptoms/risk factors, adds to unnecessary costs and delays treatment initiation. Our study aimed to determine the pre-treatment LVEF assessment practices in AYA lymphoma patients treated with anthracyclines and its association with long-term cardiotoxicity. Methods: AYA survivors diagnosed with lymphoma > 5 years ago and treated with anthracyclines at age 15-39 years were identified in a retrospective single institution registry. To ensure adequate follow-up, at least 2 follow-up visits during 2015-19 were required. Data abstracted on eligible subjects included documentation of pre-treatment LVEF evaluation, clinical rationale and treatment regimen. CV risk factors and events were collected pre-treatment and during follow-up. Descriptive statistics were used to summarize data. Results: 64/115 (56%) of AYA lymphoma patients underwent pre-treatment LVEF assessment. Rationale for/against LVEF assessment was rarely documented: low CV risk was recorded as rationale for no LVEF assessment in 2 subjects. Among AYAs who underwent pre-treatment LVEF assessment, no significant abnormalities were detected and no changes in subsequent treatment plans were found. During median follow-up of 6.7 (inter-quartile range 5.4-9.5) years, 6/115 (5%) experienced CV events. Only 2 (1.7%) survivors experienced potential anthracycline-related CV events: 1 moderate cardiomyopathy at 9 years, 1 peri-partum cardiomyopathy and atrial fibrillation due to post-radiation SVC occlusion at 15 years post-treatment. Both these AYAs (aged 38 and 31 years at time of CV events) also had other CV risk factors- family history, smoking, obesity, and hyperlipidemia. Four (3.5%) survivors’ experienced CV events (1 sinus tachyarrhythmia, 1 junctional rhythm, 2 acute/asymptomatic drop in LVEF) unrelated to anthracyclines with clear alternative etiology e.g. sepsis/symptom burden. There was no correlation between having pre-treatment LVEF assessment and occurrence of CV events. 13/115 (11.3%) developed new CV risk factors: 4 hypertension, 6 hyperlipidemia, 3 diabetes. Conclusions: Pre-treatment LVEF assessment is done inconsistently in AYA lymphoma patients but does not impact initial treatment or predict late cardiotoxicity. CV events in long-term AYA lymphoma survivors are rare but evaluation of CV risk factors, early detection and management may be more important than focusing on LVEF assessment.