bluuebunny/crossref_metadata_2025_split huggingface dataset:
Females as surgical oncologists in Taiwan: A nationwide population-based study.
Authors: Cheng Weiming , Fan Yu-Hua 
Published: May 2020

11042 Background: Operations for malignancy are stereotypically viewed as the field of men, especially in eastern countries. In recent decades, more and more women devoted themselves to be surgical oncologists. However, they face many challenges, especially when they treating patients with sex organ-related malignancies. In the present study, we compared the disparities between female and male surgical oncologists in urology, general surgery, and gynecology by analyzing a nationwide, population-based database in Taiwan. Methods: National Health Insurance covers more than 99.6% of population in Taiwan. The system’s claim data are released as the National Health Insurance Research Database. One of its database, the Longitudinal Health Insurance Database 2000, contains all the original data of one million randomly-selected beneficiaries enrolled in year 2000. We recruited the yearly inpatient and outpatient service volumes, oncological surgical volumes, revenue, and sex ratio of patients of each female and male attending general surgeons, gynecologists, and urologists with practice more than five years from 1995 to 2013. The differences of these factors between male and female physicians in each specialty were compared with Mann-Whitney U-test. P < 0.05 was viewed as statistically significant. Results: There are 13, 87, and 191 female urologists, general surgeons, and gynecologists included, accounting for 6.7%, 7.0%, and 51.3% of physicians in each specialty in Taiwan respectively. Female urologists and general surgeons had significantly more female patients (p = 0.004 and < 0.001 respectively). Female urologists had insignificantly less patient service numbers, oncological surgical volumes, and revenues (p = 0.285, 0.718, 0.077 respectively), while female general surgeons and gynecologists performed worse than corresponding male physicians (all p value < 0.001). Of noted, female general surgeons have significantly less patient service (66.0±57.1 vs. 94.8±98.9 patients, p < 0.001) and total surgical volumes (2.30±2.50 vs. 3.28±3.33 surgeries, p = 0.001) but more oncological surgeries (0.33±0.64 vs. 0.17±0.41 surgeries, p = 0.003); however, there is no differences after exclusion of surgeries for breast cancer (0.07±0.22 vs. 0.12±0.32 surgeries, p = 0.057). Conclusions: Patients tend to seek medical help from same-sex physicians in Taiwan. Females could have a comparable career with males in urology, while gender inequality remains significant in general surgery and gynecology. Female surgical oncologists may have advantages in breast cancer treatment.
A Ib/II study of the combination of lenvatinib (L) and eribulin (E) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS) (LEADER).
Authors: Chen Tom Wei-Wu , Yu Chih-Wei , Hong Ruey-Long , Yen Chueh-Chuan , Guo Jhe-Cyuan , Chen San-Chi , Lee Jen-chieh , Chen Mei-Lu , Chang Hsin-Fang , Hsu Meng-Chi , Kung Ting-Fang 
Published: May 2020

11507 Background: For advanced LPS and LMS, the two most common histologies in soft tissue sarcoma, there are limited treatment options that readily balance efficacy and toxicity. Patients (pts) treated with E had an improved median overall survival (OS) in a phase III randomized study compared to dacarbazine but with an unsatisfactory 4% objective response rate (ORR). Early studies of L, a multi-targeted anti-angiogenic inhibitor, had suggested efficacy in sarcoma pts. We hypothesized that the combination of anti-angiogenic agent and chemotherapy could potentiate treatment benefit and aimed to explore the safety and efficacy of L + E in advanced LMS and LPS. Methods: LEADER was a single-arm phase Ib/II study for advanced adult LMS and LPS pts who had received no more than 2 lines of systemic chemotherapy. The phase Ib part (starting dose: L 18mg/day, E 1.1mg/m2) had been reported and the recommended phase 2 dose (RP2D) was determined at L 14mg/day and E 1.1mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was ORR by RECIST 1.1, secondary endpoints included ORR by Choi criteria, progression-free survival (PFS), 6-month PFS rate, and OS. With α = 0.05 and 80% power, the pts needed for stage I and total of the Simon 2-stage design was 13 and 27 pts, respectively. Results: As of Jan 22, 2020, 20 pts (F/M 13/7) had been treated with at least one cycle of L + E; 14 were LMS (5 uterine, 9 non-uterine) and 6 were LPS (4 dedifferentiated, 2 myxoid round cell). The median age was 51 (range 29-73); the median lines of treatment(s) received before enrollment was 1 (range 0-3). 18 pts were evaluable for primary endpoint: the ORR by RECIST 1.1 was 27 % (5/18) (95% CI 10-53%). The ORR by Choi criteria was 67 % (12/18) (95% CI 41-87%). With 8 PFS events, the median PFS and 6-month PFS rate was 56 weeks (95% CI 25-not reached) and 72%, respectively. There were no OS events. The ORRs by RECIST 1.1 between different L starting doses were not significantly different (18mg 33% (2/6) vs 14mg 25% (3/12), p = 0.7). 15 pts experienced at-least one grade (gr) 3 or 4 adverse event (AE); gr 3 or 4 AEs occurred in > 1 pts included (% of phase Ib, % of phase II pts) hypertension (n = 4) (67%, 0%); hand-foot-syndrome (n = 4) (50%, 7%), proteinuria (n = 3) (0%, 25%), febrile neutropenia (n = 2) (17% vs 5%), neutropenia (n = 6) (50% vs 25%). The RP2D was associated with overall lower gr3/4 AEs except for proteinuria. Conclusions: L + E had shown promising efficacy in advanced LMS and LPS. L at 14mg/day had a better AE profile without compromising activity. The exploratory biomarker study of LEADER is ongoing. Clinical trial information: NCT03526679 .
A phase II study of oraxol in the treatment of unresectable cutaneous angiosarcoma.
Authors: Ravi Vinod , Wagner Michael , Chen Tom Wei-Wu , Loong Herbert H. F. , Mennel Robert Gary , Yen Chueh-Chuan , Clack Glen , Cutler David , Kwan Min-Fun Rudolf , Chan Wing Kai 
Published: May 2020

11517 Background: Oraxol is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, HM30181A. Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment. Methods: This is an open label study evaluating the activity, safety and tolerability of Oraxol 205mg/m2 administered orally, once daily, for 3 consecutive days per week. Planned treatment is for 25 weeks. Subjects included in this study had not received prior therapy with a taxane and did not have metastatic disease. Tumour response was evaluated at 6 weekly intervals using RECIST and photography. A Simon two stage design was used. Results: 18 of 24 enrolled patients (pts); male/female 11/7; median age 77 years (range 56-93), were evaluable at time of analysis. Subjects were recruited during an 18 month period, from Aug-2018 to Jan-2020. Best objective response rates were: CR 22% (n = 4), PR 11% (n = 2), SD 67% (n = 12), PD 0%. 42% of pts with SD had durability > 13 weeks (range 13-25). Median PFS was 38 weeks. All pts remain alive at time of reporting. Furthermore, 5 pts (28%) who had inoperable lesions were deemed operable after Oraxol and received surgical resection. Oraxol was generally well tolerated. Most common adverse events (AEs) G>3 were: diarrhea (n = 1), fatigue (n = 3), neutropenia (n = 9), leucopenia (n = 5), lymphopenia (n = 5). Serious AEs were G3 pneumonia in 2 subjects and G4 neutropenia in 2 subjects, one of which was febrile. All events fully resolved. Neuropathy was uncommon: n = 2 (G1 = 1 @ day 10, G2 = 1 @ day 64). Dose reductions were recorded in 7 subjects. 2 subjects discontinued treatment due to AEs; both asymptomatic pneumonitis seen on CT, which recovered after discontinuation. Following the initial positive results, the protocol has been amended to change the maximum recruitment of subjects from 25 to 43. Conclusions: Oraxol provides an orally administered treatment option for angiosarcoma, with a high and durable clinical benefit rate (CR + PR+ long SD). It is generally well tolerated even in an older patient population; particularly with respect to the the low incidence of neuropathy compared to IV paclitaxel. Recruitment is ongoing. Clinical trial information: NCT03544567 . [Table: see text]
Differential genomic landscape of clinically advanced/metastatic chordomas (mChor) based on primary tumor site.
Authors: Killian Jonathan Keith , Yang Xiaohong Rose , Danziger Natalie , Elvin Julia Andrea , Vergilio Jo-Anne , Lin Douglas I. , Williams Erik Abraham , Ramkissoon Shakti H. , Severson Eric Allan , Hemmerich Amanda , Duncan Daniel , Edgerly Claire I. , Huang Richard , Hiemenz Matthew , Reddy Venkataprasanth P. , McGregor Kimberly , Venstrom Jeffrey , Schrock Alexa Betzig , Alexander Brian Michael , Ross Jeffrey S. 
Published: May 2020

11521 Background: We queried whether comprehensive genomic profiling (CGP) could differentiate genomic alteration (GA) differences in mChor based on tumor site of origin Methods: 111 mChor FFPE tissues were sequenced using a hybrid-capture based CGP method to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: 27 clivus (Cliv), 12 cervical (Cerv), 10 thoracic (Thor) and 44 lumbosacral (Sacr) mChor were compared (Table). A separate set of 18 mChor were submitted as metastasis biopsies with no primary tumor site available (Unk). mChor was generally more common in men with Sacr tumors. Cliv patients were significantly younger (p = 0.00002). GA/tumor was highest in Sacr at 2.9 and lowest Thor at 1.5. All (100%) mChor were MSI stable and the TMB was low ( < 5 mut/Mb) for all cases. CDKN2A and CDKN2B mutation frequencies were highest in Sacr (52% and 46%, p = 0.009 and 0.0109). Potentially actionable GA in PTEN were highest in Thor and Sacr. PTCH1 GA were seen in Cliv and Cerv and PBRM1 GA potentially associated with immune-oncology (IO) drug response were present in all groups. Additional noteworthy targets were seen in all groups but were found in less than 11% of cases throughout the study (Table). Conclusions: Genomic profiles of our mChor cohort differ based on the site of tumor origin in the axial spine. Sacr appear to have the highest frequency of GA and the greatest number of potentially targetable GA. Although MSI and TMB biomarker results do not predict responsiveness, a significant PBRM1 GA frequency in all groups raises the possibility of IO drug benefit for some patients. [Table: see text]
Characterizing the landscape of genomic variants in high-risk pediatric osteosarcoma.
Authors: Marinoff Amanda , Spurr Liam F. , Doan Duong , Corson Laura , Ward Abigail , Li Yvonne Y. , Cherniack Andrew D. , Janeway Katherine A. 
Published: May 2020

11530 Background: Survival rates for patients with metastatic and/or recurrent osteosarcoma are poor, and treatment strategies have remained unchanged for more than three decades. Genomic characterization can identify new treatment strategies and improve risk stratification. To date, sequencing studies of osteosarcoma have focused on newly diagnosed patients. We present one of the first reports of osteosarcoma genomics in a high-risk cohort. Methods: 92 samples from 92 patients were sequenced in a CLIA/CAP laboratory with a targeted NGS panel test. Patients were enrolled in one of two studies. The PROFILE study enrolls all patients seen at Dana-Farber Cancer Institute, and the GAIN study enrolls patients with metastatic and/or recurrent cancer at 11 institutions. Sequencing was performed using primary tumor samples at biopsy and/or from sites of metastasis when available. Results: 33 patients were enrolled on the PROFILE study, and 59 were enrolled on GAIN. Diagnostic stage was available for 65 (67%) of patients. 37% had metastatic disease at diagnosis. The 3-year overall survival (OS) was 71% for the entire study population, 56% for patients with metastatic disease at diagnosis, and 81% for patients with initially localized disease. The presence of metastases at diagnosis was significantly associated with poor outcome (p < 0.0087) and was the only independent clinical prognostic factor identified. Genomic analysis revealed frequent alterations in TP53 (37%), RB1 (15%), CDKN2A (13%), MYC (12%), CDKN1A (12%), ATRX (10%), and CCND3 (8%). Patients whose tumors had MYC amplification (defined as ≥ 6 copies) had a 3-year OS of 39% compared with a 3-year OS of 76% in the absence of MYC amplification, a difference with borderline statistical significance (p = 0.051). Conclusions: In the first study to examine genomic alterations detected by targeted gene panel sequencing in a CAP-certified laboratory in a large population of pediatric patients with higher risk osteosarcoma, the most frequently occurring events were similar to those found in prior reports. MYC amplification, reported as a possible poor prognostic factor in other studies, was present in 12% of patients and was associated with a worse OS, though this finding did not reach statistical significance.
Outcomes of patients (pts) with advanced gastro-intestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib (IM) as first-line treatment.
Authors: Boileve Alice , Dufresne Armelle , Chamseddine Ali N. , Dumont Sarah Naomie , Brahmi Medhi , Adam Julien , Rouleau Etienne , Karanian Marie , Haddad Veronique , Faron Matthieu , Honoré Charles , Meeus Pierre , Le Cesne Axel , Blay Jean-Yves , Mir Olivier 
Published: May 2020

11532 Background: IM is the standard first-line therapy in advanced GIST, with a median progression-free survival (PFS) of 30 months. Recent multi-kinase inhibitors (MKIs) such as nilotinib, dasatinib or masitinib have been tested as first-line therapies in phase II/III studies. This might theoretically result in increased PFS (by the addition of a new line of treatment), or in early emergence of resistance to approved MKIs. Methods: A retrospective chart review was performed in GIST pts who received investigational MKIs (in phase II/III trials) as first-line treatment, followed by IM as second line. Data on demographics, molecular profile, PFS, and overall survival (OS) were collected in two French referral centers. Results: Of 47 pts, (57% females), 22 (47%) had a KIT exon 11 mutation, one a KIT exon 9 mutation (2%), one a PDGFR D842V mutation (2%). Five patients were wild-type for KIT and PDGFR. The mutational status was unknown in 18 pts (38 %). From 2005 to 2011, 21 pts (45%) received masitinib, 18 (38%) received dasatinib and 8 pts (17%) received nilotinib. Median PFS on first-line treatment was 18.9 months [95%IC: 9.0-26.0]. Median time-to-failure (TTF) with IM was 19.7 months [95%IC: 14.8-53.4]. Median time to second relapse was 50.2 months [95%IC: 31.2-92.2]. Thirty-five patients (74.5%) were dead at the end of follow-up. The median OS from time of initial diagnosis was 5.9 years [95%IC: 4.5-8.2]. Conclusions: GIST pts who received MKIs other than IM as first-line treatment and IM as second-line had a time to second relapse longer than that observed historically with IM in first line. This suggests that using MKIs other than IM in first line does not decrease IM efficacy in second line. Further comparative studies are needed to confirm these findings, but this is encouraging to further develop studies with other MKIs in the first line setting.
Identification of SDHA germline mutations in sporadic SDHA mutant gastrointestinal stromal tumors (GIST): The need of a genetic counselling.
Authors: Nannini Margherita , Urbini Milena , Indio Valentina , Schipani Angela , Vincenzi Bruno , Silletta Marianna , Grignani Giovanni , Tolomeo Francesco , Rizzo Alessandro , Fumagalli Elena , Conca Elena , Saponara Maristella , Astolfi Annalisa , Pantaleo Maria A. 
Published: May 2020

11537 Background: SDH- deficient GIST, as defined by the loss of expression of SDHB, account up to about 10% of all gastric GIST and generally affect younger population. Germline mutations in SDHB, SDHC, and SDHD occur in about 20–30% of SDH- deficient, that may be referred to a hereditary condition known as hereditary GIST-paraganglioma syndrome (Carney-Stratakis Syndrome), whereas germline SDHA mutations have been rarely described in apparently sporadic cases. Currently, even germline testing is recommended for SDH- deficient GIST, there are no clear guidelines for genetic counselling and follow-up of SDH x mutation carriers and relatives, especially for SDHA mutant GIST not yet linked to well-defined hereditary syndrome. The aim of this work was to study the SDHA gene in the normal DNA of patients with SDHA mutant GIST. Methods: Thirteen patients carrying SDHA-mutant GIST were studied (8F/5M). Median age of diagnosis was 45,9 years (range 25-74). All GIST were located in the stomach and 3 patients out 13 presented a metastatic disease. In all cases except one, the GIST was the only cancer presentation and no personal or familial history of cancer was revealed. All cases were negative for SDHB immunohistochemistry. Germline mutations were identified through Sanger sequencing of SDHA in the normal counterpart. Results: Germline mutations were identified in all patients for which normal counterpart was available: 4 cases harboured truncating mutations (S384X, R31X and W119X); 5 cases carried pathogenic missense mutations (G233V, R171H, R589Q, G257A and R600Q) and 2 cases had splice site alterations (c.457-3_457-1 delCAG and c.456+9 C > T). In 8 cases the tumor DNA showed the loss of the corresponding wild-type allele, while in the other 3 cases compound heterozygosity for an additional somatic mutation was detected (R589W, R451C,and R171C). In 2 patients, unfortunately, normal DNA was not available, however both tumours carried two mutational hits on SDHA (one with heterozygous G419R and E564K, and one with homozygous R585Q). Of note, 5 patients presented un-usaul SDHA related clinical characteristics as were not young adult ( > 50 years-old) or no multifocal GIST. Conclusions: We demonstrated that germline SDHA mutations are highly frequent in SDHA- deficient GIST. Therefore, although a clear syndrome has not been defined, genetic counselling and follow-up of SDHA mutation carriers and relatives should be clarified.
Efficacy and safety of hypofractionated preoperative radiotherapy in treatment of patient with primary locally advanced soft tissue sarcoma of limbs/trunk wall.
Authors: Kosela Hanna , Spalek Mateusz , Borkowska Aneta , Teterycz Pawel , Morysinski Tadeusz , Wagrodzki Michal , Goryn Tomasz , Zdzienicki Marcin , Rutkowski Piotr 
Published: May 2020

11555 Background: Soft tissue sarcomas (STS) are rare often malignant tumors. The primary treatment of most STS is radical resection with adjuvant radiotherapy. Our previous study showed that the use of preoperative hypofractionated radiotherapy is safe and efficient in the treatment of unselected group of patients with STS. Aim of this study was to assess the use of the treatment scheme in patients with primary STS treated in one institution. Methods: 311 patients (52% female) with primary locally advanced STS participated in this prospective trial conducted from 2010 till 2017. Median age was 55 years (range: 17-91). Median follow up is 57 months (95%CI 55-61). The most common subtypes were pleomorphic sarcoma, liposarcoma and synovial sarcoma. Median tumor size was 11cm. 258 patients (83%) had high grade tumors. The most common tumor localization were lower limbs (72%). 30% of patients received preoperative chemotherapy. For five consecutive days radiotherapy in 5 x 5Gy fraction was applied, with immediate (2-4 days) resection of the tumor. Results: In 260 patients (83.6%) clear surgical margins (R0) were obtained. 107 patients were dead at the time of the analysis.5-year overall survival is 63%. 156 (50%) had a recurrence of the disease. Local recurrence (LR) was found in 13.8% of the patients. Median time from surgery to LR was 14.7 months. In 56% of patients with LR another limb spearing radical surgery could be performed. Factors that had a significant adverse impact on LR were histological subtype (p = 0.017) and surgical margin status (p = 0.013). Factors that had a significant adverse impact on overall survival were tumor size (p < 0.0001), grade (p = 0.0047) and surgical margin status (p = 0.013). 96 patients (30.8%) had any kind of treatment toxicity, factor having negative impact on the toxicity was lower limb location of the tumor (p = 0.0012). 20 patients (6.4%) required surgery for treatment of the complications. 14.6% patients had prolonged healing of the wound ( > 1 month), 8.3% had wound dehiscence, 1.4% required prolonged punctures of the lymph fluid, 2.3% had severe fibrosis leading to contracture of limb, 11% patients prolonged edema of the operated limb. 0.9% of patients had a fracture of the treated limb. Conclusions: In this group, with a big percentage of patients with large, high grade STS use of hypofractionated preoperative radiotherapy was associated with similar local control when compared to published studies. The early toxicity is tolerable, with a small amount of late complications.
ACUFOCIN: Randomized clinical trial of ACUpuncture plus standard care versus standard care alone FOr Chemotherapy Induced peripheral Neuropathy (CIPN).
Authors: Wardley Andrew M. , Ryder David , Misra Vivek , Hall Peter S , Mackereth Peter , Stringer Jacqui 
Published: May 2020

12003 Background: CIPN is a dose limiting toxicity, and a major clinical challenge. This study aims to explore the use of acupuncture with standard care (Acu +SC) against SC alone, to reduce symptoms of CIPN. Methods: A phase II, randomised, parallel group design was used to investigate the effectiveness of a 10 week course of acupuncture to manage CIPN. Patients experiencing CIPN ≥ Grade II (CTCAE v4.03), recording a ‘Most Troublesome’ CIPN symptom score of ≥ 3 using the "Measure Yourself Medical Outcome Profile" (MYMOP 2), were randomised (1:1) to either Acu+SC or SC alone. The primary end-point was a ≥ 2 point improvement in MYMOP2 score at week 10 (logistic regression adjusted for stratification factors and baseline MYMOP2 score). The necessary sample size was 100 patients;120 were randomised to allow for attrition (90% power; 10% one-sided alpha), for a hypothesised improvement in success proportions from 30% to 55%. Results: 120 patients were randomised to ACUFOCIN; diagnosis: breast 61 (51%), multiple myeloma 9 (8%), GI 48 (40%), gynaecological 2 (2%). MYMOP2 score for most troubling CIPN symptom at baseline: 3-4 33 (28%), 5-6 87 (73%). CTCAE CIPN at baseline; grade II 103 (86%), grade III 17 (14%). Baseline characteristics were balanced between arms. Primary outcome data were available for 108 participants with 36/54 (67%) successes in the Acu+SC arm compared to 18/55 (33%) in the SC arm. Adjusted success odds ratio was 4.3 (95% CI 1.9-9.6; p < 0.001; Acu+SC vs SC). Additionally, 27/53 (51%) participants achieved a CIPN success (grade ≤ I) in the Acu+SC arm compared to 4/56 (7%) in the SC arm with adjusted odds ratio 13.1 (95% CI 4.1-41.7; p < 0.001; Acu+SC vs SC). Significant reduction in week 10 pain score; mean difference (SC+Acu – SC alone) -1.45 with 95% CI (-2.25, -0.65) after adjustment for week 1 pain, breast cancer diagnosis and treatment complete status. (note pain on a 0-10 scale). Significant increase in the EORTC QLQ-C30 summary score; mean difference (SC+Acu – SC alone) 9.51 with 95% CI (5.01, 14.02) after adjustment for the baseline score, breast cancer diagnosis and treatment complete status. (note summary score on a 0-100 scale). Significant effects seen at week 10 are also present at week 6. The week 6 effect estimates are consistently less than the week 10 effects (but not usually statistically significantly so). Conclusions: In this patient cohort, a 10 week course of acupuncture significantly improved symptoms of CIPN. These results support further investigation within a phase III trial. Clinical trial information: NCT02275403 .