bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of anlotinib in advanced soft tissue sarcoma: results from one of multi-centers in a phase IIB trial (ALTER0203).
Authors: Tang Lina , Wang Yonggang , Zhang Jianjun , Yu Wenxi , Huang Yujing , Yao Yang 
Published: March 2020

e22518 Background: There is no standard therapy for soft tissue sarcoma (STS) patients progressing after first-line chemotherapy. Anlotinib significantly prolonged PFS in advanced STS patients in the earlier results of ALTER0203. In view of regional differences, we further analysis results from Affiliated Sixth People’s Hospital, Shanghai Jiaotong University, one center in this IIB trial. Methods: Patients aged from 18 to 70 with advanced STS, progressing after anthracycline-based chemotherapy (not adapted to alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CSC)), angiogenesis inhibitor naive, at least one measurable lesion according to RECIST 1.1, were eligible. Patients were randomised in a 2:1 ratio to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. Primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR). Results: This center of ALTER0203 enrolled 48 eligible patients who received either anlotinib (n = 32) or placebo (n = 16). Leiomyosarcoma (LMS) (13/48), ASPS (12/48), synovial sarcoma (SS) (11/48) were major subtypes. The median PFS was 1.57 months (95% CI: 1.19-1.95) for placebo versus 6.27 months (95% CI: 1.89-10.65) for anlotinib ( P= 0.009). ORR was 0% (0/16) for placebo versus 18.75% (6/32) for anlotinib ( P= 0.16); DCR was 18.75% (3/16) for placebo versus 56.25% (18/32) for anlotinib ( P= 0.02). The most common adverse events (AEs) were hypertension, elevated TSH, hypertriglyceridaemia (HTG). The most common Grade ≥3 AEs were menstrual disorder, hypertension, gamma glutamyl transferase (GGT) elevation and lipase elevation. Conclusions: The efficacy and safety of anlotinib is further confirmed in advanced STS patients regarding regional differences. Clinical trial information: NCT02449343. [Table: see text]
The phase Ib result of the safety and efficacy of lenvatinib (lenv) plus eribulin (eri) in advanced adipocytic sarcoma (LPS) and leiomyosarcoma (LMS): LEADER study (NCT03526679).
Authors: Chen Tom Wei-Wu , Hong Ruey-Long , Yen Chueh-Chuan , Chen San-Chi , Guo Jhe-Cyuan , Hsu Meng-Chi , Kung Ting-Fang 
Published: March 2020

e22524 Background: Eri, although approved for advanced LPS, has limited activity in terms of tumor shrinkage. Anti-angiogenic agents have shown to increase tumor response in certain cancer types. This study aims to understand the safety, optimal dose, and efficacy of the combination of lenv, a multi-kinase anti-angiogenic inhibitor, and eri in LMS and LPS. Methods: Advanced LMS and LPS with no more than 2 lines of systemic chemotherapy were eligible. The starting dose was lenv 18mg/day daily and eri 1.1mg/m2 D1, D8 in a 21-day cycle. The primary endpoint of the phase Ib part was to assess the dose-limiting toxicity (DLT) in the first 21 days and to determine the recommended phase II dose (RP2D). A rule-based (≤ 33% DLT in first 6 pts) design was implemented in the phase Ib part. Results: From 2018 Jul 24 to 2019 Jan 8, a total of 6 pts (4 LMS, 1 dedifferentiated LPS, 1 myxoid LPS) were enrolled. The median age was 56 (range 30-70), female: male 3:3. Only 1 pt had a DLT, which was < 75% of the planned dosage. Within all (27) cycles, common grade (gr) 3 or higher adverse events (AE) included hypertension (HTN, n = 4), hand-foot syndrome (HFS, n = 3), and neutropenia (n = 4). However, 4 pts had late-onset gr3 or multiple coexisting gr2 AEs that necessitated dose reduction(s) (dr) for lenv (7 dr) or eri (2 dr) after the DLT assessment period (see table). The median time to 14 mg/day, 10mg/day of lenv, and eri 0.7mg/m2 was 22, 28 (after starting lenv 14mg/day), and 69 days, respectively. In terms of preliminary anti-tumor activity, 5 (83%) pts had target lesion shrinkage and 2 (33%) reached PR (1 confirmed) as best response according to RECIST 1.1. Conclusions: Late-onset AEs after cycle 1 leading to dose reduction was notable for lenv + eri and the RP2D was thus determined at a lower starting dose of lenv 14mg/day and eri 1.1mg/m2. The preliminary tumor response was also promising. Efficacy and safety of lenv + eri for LMS and LPS will continue to be explored in phase II study. Clinical trial information: NCT03526679. [Table: see text]
Outcomes of advanced angiosarcoma and hemangioendothelioma on propranolol based regimens from sarcoma medical oncology clinic in North India.
Authors: G Naresh , Rastogi Sameer , Barwad Adarsh , Dhamija Ekta , van Houdt Winan J. , Steeghs Neeltje , Panday Rambha , Aggarwal Aditi , Garg Rakesh 
Published: March 2020

e22539 Background: Angiosarcoma is an extremely rare subtype of soft tissue sarcoma with a dismal prognosis. The response rate with current standard treatment is low and new approaches are needed. Propranolol is a well-known, generic ß-blocker that has recently been approved for the treatment of a benign vascular tumor, hemangioma, with high response rates. Several preclinical studies and case reports suggest that propranolol could also be repurposed to treat malignant vascular tumors like angiosarcoma. Methods: All patients with advanced or unresectable angiosarcoma and hemangioendothelioma that were treated in the Sarcoma medical oncology clinic in North India from January 2016 to August 2018 were included. Patients were treated with 40 mg BID propranolol with or without chemotherapy or targeted agents. Results: Eight patients with angiosarcoma or hemangioendothelioma were treated with propranolol in combination with pazopanib, methotrexate and vinblastine or methotrexate monotherapy. The median follow up period was 15 months, response rates were 14%. Median PFS was not reached, but the 10 months PFS was 60%. Median OS was not reached, but the 10 months OS was 80%. Conclusions: Treatment of angiosarcoma or hemangioendothelioma patients with propranolol in combination with chemotherapy or targeted therapy shows promising results in terms of survival albeit with relatively low response rates .To determine the exact place of propranolol in the treatment of angiosarcoma, more patients need to be treated, the efficacy of propranolol as monotherapy needs to be evaluated and the role of β-adrenergic receptor as a predictive biomarker needs to be clarified further. Additionally, different combination partners should be tested to determine the optimal backbone for the combination therapy with propranolol.
Desmoid tumor (DT) management in dedicated sarcoma medical oncology clinic in a developing country: Lessons learnt.
Authors: Rastogi Sameer , Aggarwal Aditi , Dhamija Ekta , Barwad Adarsh , Panday Rambha , Khan Shah Alam , Sampat kumar Venkat , Shishak Sorun , Kumar C Santosh , Deo Svs , Manasa Parisa , Kapoor Rashi , Kumar Pankaj 
Published: March 2020

e22541 Background: There is lack of data about desmoid tumors from India except case reports. It is not known how these patients are dealt with outside tertiary care centres who lack expertise. Methods: We retrospectively analysed all patients of DT from a prospectively maintained database who were referred to AIIMS Sarcoma Medical Oncology Clinic from January 2016 till 2019. Results: There were total of 56 patients with male: female ratio of 3:4. Median age was 26 (3-57) years. Extremity was most common site (57%) and median tumour size was 12 (range 3-20) cm. One patient (1.8%) had FAP and 1 (1.8%) had multifocal disease. A total of 27 patients received first treatment outside our institute and was primary surgery in all (100%). However, of the remaining 29 patients who primarily presented to us, surgery was done only in 3 (10%) because of patients choice and pelvic location. Five patients were kept under observation and all are doing well. Tamoxifen with celecoxib was most common first line therapy in 80% (40/50) with other options being sorafenib (6/50) and chemotherapy (4/50). Chemotherapy was used in abdomen (3/4) and head neck (1/4) primary patients. Menstrual irregularities including amenorrhoea was most common toxicity in 33% (13/40) with tamoxifen combination and a cause of concern in this cohort of young females leading to discontinuation of therapy inspite of SD in 54% (7/13) patients. Second line therapy was started in 20 patients with sorafenib being most common (13/20), others being chemotherapy (4/20), tamoxifen combination (2/20) and imatinib (1/20). Of all 19 patients on sorafenib, 10 (53%) experienced Hand Foot Syndrome. None discontinued sorafenib due to HFS. After median follow up of 15 months, median progression free survival (PFS) with first line was 29 months (11-46) and with second line it was not reached. There have been three deaths till date (5.3%), all were non-extremity primaries. Conclusions: In Indian setup, majority of patients presenting outside tertiary care centre undergo surgery as the first line therapy without any inclusion of medical therapy. This might be attributed to lack of awareness about medical therapy and natural trajectory of disease. Tamoxifen though was a commonly used option, led to toxicity which is of concern in young Indian patients leading to discontinuation. Sorafenib is well tolerable except HFS but longer follow up is needed for efficacy analysis.
Molecular characterization and management of secondary resistance to serial TRK inhibitors.
Authors: Nathenson Michael , Hemming Matthew Louis , Malik Karan , Lin Jia-Ren , Santagata Sandro , Du Ziming , Marino-Enriquez Adrian , Hagan Timothy J , Chipashvili Otari , Thornton Katherine Anne , Raut Chandrajit P. , Childs Barrett H. , Bertagnolli Monica M. , Sicinska Ewa , Ku Nora , Demetri George D. 
Published: March 2020

e22547 Background: TRK inhibitor drugs such as the highly selective larotrectinib (Laro), have proven highly effective in malignancies harboring fusions of NTRK1, 2, or 3. Resistance in patients (pts) with progressive disease (PD) after response to initial TRK inhibitor therapy has been attributed to secondary mutations in the solvent front or gatekeeper domains of the NTRK fusion gene. LOXO-195 (L195) is a 2nd generation TRK inhibitor that overcomes these mutations. Mechanisms of resistance to L195 have not yet been well characterized. Methods: We analyzed molecular mechanisms of resistance in one adult pt with undifferentiated pleomorphic sarcoma (UPS) who had serial responses and PD on Laro and L195. Targeted DNA sequencing, RNA sequencing and multicolor cyclic immunofluorescence (CyCIF) were performed on pre- and post-PD specimens on both drugs. Results: The patient was enrolled on the phase 2 clinical trial of Laro (NCT02576431) with TPM3-NTRK1 fusion UPS. Multifocal PD and resistance to Laro developed after major objective response RECIST -74.9%, of 10 months (mo); the resistant tumor harbored both the initial TPM3-NTRK1 fusion but also evolved a new solvent front mutation in NTRK1 [c.1783G > A (p.G595R)]. A single pt protocol (NCT03206931) was designed to treat with L195. After an initial response to L195, PD limited to 2 sites developed; both sites were resected at 5 and 10 mo. The pt continues on L195 with systemic disease control 20 mo after initiation (in total 30 mo since Laro initiation). Analysis of tumor samples pre- and post-PD on L195 identified the emergence of a KRAS G12V mutation, with associated activation of the KRAS signaling pathway and a significant infiltration by inflammatory cells. A cell line and pt-derived xenografts (PDX), all harboring the initial TPM3-NTRK1 fusion, were generated from this pt. Conclusions: Resection of oligoclonal PD and continuation of L195 post-PD can be an effective treatment strategy. Oncogenic activation of the KRAS pathway is a possible mechanism of resistance to L195. Our studies indicate that the tumor microenvironment of TRK-fusion sarcomas resistant to TRK inhibitors may increase inflammatory cell infiltrates, which may provide clues for future combination therapy.
Clinical features and prognosis of patients with liposarcoma: Single-center experience.
Authors: Demir Metin , Guven Deniz Can , Aktas Burak Yasin , Güner Gürkan , Aktepe Oktay Halit , Taban Hakan , Kilickap Saadettin , Kars Ayse , Turker Alev , Yalcin Suayib , Dizdar Omer 
Published: March 2020

e22557 Background: Liposarcomas constitute 15% of all soft tissue sarcomas.They consist of four subtypes;well-differentiated,dedifferentiated,myxoid and pleomorphic.In this trial we assessed demographic and clinical features of patients with liposarcoma who were treated in our hospital.Methods: Patients who were diagnosed with liposarcoma in Hacettepe University Medical Oncology Department between 2005and2015(n = 119) were included. Patients’ data were collected from hospital registration system.Survival analyses were performed with Kaplan Meier analyses.Results: At the time of diagnosis, the vast majority of patients had localized and/or node positive disease(n = 98),8 patients had metastatic disease.Further analyses hold for only early stage disease:Median age was 52(min:18-max:81).105 patients(94.6%) had upfront surgery.26(23.4%) and 30 patients(27%) received perioperative chemotherapy(CT) and radiotherapy(RT),respectively.The most commonly used CT agents were ifosfamide, anthracyclines, etoposide,taxanes and gemcitabine.At a median follow-up of 45months, relapses were observed in 34 patients(30.6%) and 35 patients(31.5%) died.Median overall survival(OS) was 113.1 months and median relapse free survival (RFS) was 23.8 months.Perioperative CT and RT were not associated with improved RFS and OS.Among patients with early stage disease; median RFS of patients with well-differentiated, dedifferentiated, myxoid and pleomorphic subtypes were 31.8,34.3,28 and 5.2months,respectively(p = 0.013).Well-differentiated group had significantly higher RFS than those with pleomorphic liposarcomas(p = 0.003).The mostly used CT drugs in recurrent setting were ifosfamide+doxorubicine(42.9%) and ifosfamide+etoposide(21.4%).Conclusions: Liposarcoma prognosis varies significantly with histological subtype and the efficacy of systemic chemotherapy is limited both in early stage and advanced disease.[Table: see text]
Patient perceptions of treatment benefit in advanced cancer.
Authors: Patell Rushad , Einstein David Johnson , Halleck Jennifer , Buss Mary K. 
Published: March 2020

e23163 Background: Informed consent assumes accurate perceptions of potential benefits and risks of treatment, yet many patients receiving palliative cancer therapies misperceive the likelihood of cure. Our study aims to further explore patient perceptions of benefits and risks of palliative treatments and to examine this in the era of novel therapeutics. Methods: We surveyed patients with advanced solid cancers and their oncologists regarding benefits/risks of palliative therapies. We serially assessed patients’ perceptions of likelihood of tumor response, survival benefit, symptom palliation and side effects, as well as information-seeking behavior pre-treatment and decisional regret at the end of treatment. We also compared patients’ perceptions of benefits/risks to that of their oncologists. Results: Across four disease groups, 52 patients have enrolled (target accrual: 120). Median age is 64 years (range 20-84), 58% are male, and 60% had prior treatment. Treatments included chemotherapy (42%), targeted therapy (31%), and immunotherapy (27%). Misperceptions (patient-assessed likelihood minus oncologist-assessed likelihood) at the beginning of treatment across different domains are shown in the table. Conclusions: Compared with their oncologists, patients overestimate not only curability but also chance of tumor response, symptom palliation, and survival benefit, yet they accurately perceive chance of toxicity. Thus, efforts at improving communication should focus on the chances of treatment benefit and multiple types of benefits rather than treatment risks. In future analyses after full accrual, we will assess differences between domains, internal consistency of misperceptions, change in misperceptions over time on treatment, decisional regret at end of treatment, and association of misperceptions with information-seeking behavior and sources of education. [Table: see text]
Utilizing the patient-reported outcomes measurement information system (PROMIS) to assess quality of life among breast cancer patients at an academic center.
Authors: Matthys Madeline B. , Dempsey Andre , Melisko Michelle E. , Basu Amrita , Dreher Nickolas , van 't Veer Laura , Esserman Laura 
Published: March 2020

e23171 Background: NCI PROMIS assesses physical, mental and social health across multiple health conditions. Despite interest in using PROMIS in oncology trials and clinical care, reference values in cancer are not well established. Methods: Electronic intake questionnaires assessing self-reported history and 8 PROMIS domains (depression, anxiety, fatigue, sleep-related impairment (SRI), sleep disturbance, cognitive function, applied cognition and physical function) are sent to all new patients (pts). 2886 pts with self-reported breast cancer completed the questionnaire/consented to research. PROMIS T-Scores were calculated using the Health Measures system. Results: For all domains except depression, cognitive function and applied cognition, pts had clinically meaningful ( > 3 point diff.) worse mean PROMIS scores than US means (50). Compared to stage 0-III, stage IV pts had worse scores for all assessed domains (p < 0.05). Among Stage IV pts < 49, QoL was significantly worse in 7/8 domains (see table). Across all age groups, there were significant differences in mean PROMIS scores for Stage IV pts in anxiety, depression, cognitive function and applied cognition (p < 0.05). Conclusions: PROMIS scores among pts indicate impaired QoL in multiple domains. These scores provide insight into the physical, mental and social health of our pts and can serve as robust estimates for breast cancer trials and clinical care. [Table: see text]
Recommendations from clinical practice guidelines on discussion of costs of care in adult patients with advanced cancer: A systematic review.
Authors: Agarwal Anupriya , Karikios Deme John , Stockler Martin R. , Beale Philip James , Morton Rachael L. 
Published: March 2020

e23175 Background: Optimising the care of cancer patients without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The 2009 American Society of Clinical Oncology’s (ASCO) Guidance Statement on the Cost of Cancer Care recommends that ‘patient-physician discussions regarding the cost of care are an important component of high-quality care’.(1) We sought information for oncologists to facilitate patient-clinician communication about the costs of care in published clinical practice guidelines (CPGs). Methods: We searched MEDLINE, EMBASE and multiple databases of CPG from January 2008 to 1st June 2018 for recommendations about discussing the costs of care. We assessed quality with the AGREE II instrument for the assessment of guidelines. Results: We identified 471 publications, of which 25 guidelines met our eligibility criteria. Most guidelines were from ASCO (64%, 16/25) and the Scottish Intercollegiate Guidelines Network (SIGN, 24%, 6/25). Guidelines included recommendations on discussion or consideration of treatment costs when prescribing in 52% (13/25) with information about actual costs in only 20% (5/25). Recognition of the risk of financial burden or financial toxicity was described in 60% (15/25) of guidelines, however, only a minority of these, 28% (7/25) contained information regarding management of patients with financial concerns. Conclusions: Current CPGs have limited information to guide patient-clinician communication about the costs of anticancer treatment and management of financial burden. Future guidelines should contain more information about the optimal timing, frequency, and content of these discussions. Future guidelines should include more guidance about how oncologists should communicate the costs of care accurately and transparently, along with suggestions to reduce financial burden.
Therapy preference scale: A novel questionnaire to understand patients’ preferences of cancer treatment.
Authors: Bhatt Vijaya Raj , Dhakal Prajwal , Wichman Christopher S , Pozehl Bunny J 
Published: March 2020

e23179 Background: Engaging patients in shared decision-making can help select an appropriate treatment for an individual and enhance patients’ experience and satisfaction with their care. This requires an in-depth understanding of patients’ values and preferences of various aspects of cancer treatment. A questionnaire to assess patient preferences is currently lacking. The purpose of our study was to develop a questionnaire that would fill this gap. Methods: We reviewed published literature to develop a theoretical framework to explain how cancer patients chose a specific therapy for themselves, and to identify key aspects of treatment that determine patients’ decisions about treatment. Three key domains (efficacy, safety and other characteristics of treatment such as need for hospital stay) were identified (Bhatt VR, J Geriatr Oncol. 2018 Nov 27 [Epub ahead of print]) and a mutli-dimensional self-report questionnaire with 49 items was developed. Each item was rated for relevance by 10 experts (oncologists, oncology nurses, advanced practice providers, social workers and pharmacists) to assess content validity (Lawshe formula) (Meas Eval Couns Dev, 47: 79–86). Ratings of ‘very relevant’ or ‘relevant’ were used to identify an essential question. Experts also suggested refinement of items. Three community members and 9 patients evaluated the instrument for face validity. Results: A content validity index for the questionnaire was 0.82. Face validity was confirmed. Based on input from the various stakeholders, the number of items, content, and format of the questionnaire was revised. The revised questionnaire includes a total of 36 items under four sections: safety (14 items), efficacy (4 items), treatment characteristics (8 items) and global items (10 items). Conclusions: We have developed a novel tool and established content and face validity. This self-report questionnaire can be used to understand patients’ preferences of cancer treatment. Further psychometric studies are planned to evaluate reliability and validity. Our ultimate goal is to use this tool to enhance communication between physicians and patients and facilitate shared decision-making.