bluuebunny/crossref_metadata_2025_split huggingface dataset:
Where is your lactation room? Lactation policies and practices in oncology trainee and early career physicians.
Authors: Malapati Sindhu Janarthanam , Singh Sunny R K , Idossa Dame , Jordan Bruno Ximena , Chino Fumiko , Patel Monica Arun , Wei Zihan , Duma Narjust 
Published: June 2022

11054 Background: Training and early career years coincide with childbearing and raising young families, which places increased demands on new parents. With increasing numbers of female oncologists in the workforce, there is a need to assess and amend current workplace lactation policies. We surveyed Medical and Radiation Oncology trainees and early career faculty to assess policies and practices regarding lactation during training and early career. Methods: An anonymous 48 question cross-sectional survey developed by researchers with expertise in gender equity was distributed via email and social media channels between May and June 2021 to oncology trainees and physicians within 5 years of terminal training; program directors (PDs) were surveyed separately. Descriptive statistics were used. Results: Of the 255 complete responses, 26% (65) respondents breastfed for any length of time upon return to work. Of these, 54% (35) were trainees and 46% (30) early career faculty. 69% (45) had access to a designated lactation room; however, 57% (37) noted that duration of their pumping breaks was inadequate to access and use the lactation room. Most (60%, 39) did not feel comfortable asking for protected time to pump. Employment contracts did not specifically include pumping breaks for 66% (43), while 34% (22) were unsure about their contract policies surrounding lactation. Of all breastfeeding mothers, 77% (50) felt their colleagues to be supportive of their needs; a minority reported negative responses due to pumping breaks from faculty (11%), co-fellows/colleagues (8%) and clinic staff (15%). 51% (33) bought a wearable pump prior to return to work, of which 70% (23) found it financially burdensome. Most common reasons for buying a wearable pump were to improve efficiency during work hours (61%, 20) and lack of adequate pumping breaks (39%, 13). Among 23 PDs who responded to the survey, 65% (15) had a program policy regarding lactating trainees, 9% (2) blocked clinic appointments to allow pumping breaks, 91% (21) provided lactation rooms, 83% (19) reported the lactation rooms are easily accessible. Conclusions: Both infrastructure and time accommodations made for the lactating parent are inadequate. There is a disconnect between the trainee and PDs’ perception of provided accommodations. Systemic changes that provide adequate time and space for lactation to busy clinicians and trainees is imperative to ensure retention of women oncologists in the workforce.
Identifying predictors of equitable gender representation among hematology and oncology fellowship programs.
Authors: Pandravada Sasirekha , Mylavarapu Praneet , Bitran Jacob D. 
Published: June 2022

11055 Background: While gender disparities have largely been bridged among hematology and oncology fellows at the national level, there exist many individual fellowship programs that still have marked gender disparity. Our study is the first to examine gender differences among fellows at an institutional level in order to model characteristics of hematology and oncology programs that lead to more equitable gender representation. Methods: For each of the 148 hematology or oncology fellowship programs listed in the Fellowship and Residency Electronic Interactive Database, we collected data on gender, faculty academic rank, and fellow postgraduate year as listed on individual program websites. Further, a program was identified as an academic center if it had an affiliated medical school. Zip code data was used to identify geographic region, local population density, and racial diversity of each program’s surrounding neighborhood. Multiple linear regression was used to model which factors contributed to a program having a higher percentage of female fellows. Results: 3600 faculty and 1488 fellows were included in the analysis. While women were well represented nationally among fellows (46.4%), 52.4% of fellowship programs had fewer than 50% women, and 28.6% of programs had fewer than 35% women. An individual program was more likely to have more female fellows if it had a higher percentage of female assistant professors (p<0.01), associate professors (p<0.01), assistant professors overall (p<0.01), a female program director (PD) or associate program director (APD) (p=0.02), and a designation as an academic center (p<0.01). Notably, the percentage of female full professors had no significant impact (p=0.11) on whether a program was likely to have more female fellows. Conclusions: While women are well represented nationally among hematology and oncology fellows, nearly one in three fellowship programs still have significant gender disparity. Our multivariate model identified several significant factors that predict whether a program was likely to have gender parity among fellows: a higher percentage of female assistant professors, associate professors, assistant professors overall, a female PD or APD, and a designation as an academic center. Whether these factors together highlight the importance of accessible mentorship or direct female faculty role models requires further study. However, by beginning to identify these significant factors, we hope to aid fellowship programs focus efforts when trying to achieve equitable gender representation.[Table: see text]
A phase Ib/II study of the combination of lenvatinib (L) and eribulin (E) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS) (LEADER): Efficacy updates.
Authors: Chen Tom Wei-Wu , Yen Chueh-Chuan , Hong Ruey-Long , Lee Jen-Chieh , Chang Koping , Yu Chih-Wei , Chen San-Chi , Chen Mei-Lu , Hsu Meng-Chi , Kung Ting-Fang , Cheng Ann-Lii 
Published: June 2022

11506 Background: There are limited treatment options for advanced LPS and LMS, the two most common histologies in soft tissue sarcoma. Patients (pts) treated with E had an improved overall survival (OS) 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 L+E could potentiate the treatment efficacy 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 (NCT03526679). 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 progression-free survival (PFS), 6-month PFS rate, and OS. Pts in phase Ib/II part were analyzed together for efficacy. Results: As of Nov 15 2021, 30 pts (F/M 20/10) had been treated with at least one cycle of L + E; 21 were LMS (9 uterine, 12 non-uterine) and 9 were LPS (5 dedifferentiated, 2 myxoid round cell, 2 pleomorphic). The median age was 59 (range 29-73); the median lines of treatment(s) received before enrollment was 1 (range 0-3). The ORR by RECIST 1.1 was 20 % (6/30) (95% CI 10-53%); the ORR for pts received L 18mg/day (2/6) and L 14mg/day (4/26) were not significantly different (p = 0.23). After a median FU time of 20.1 months, the median PFS and 6-month PFS rate was 8.56 mos (95% CI 4.40-not reached (NR)) and 59%, respectively. The median PFS for LMS (8.56 mos, 95% CI 4.17- NR) and LPS (11.36 mos, 95% CI 4.4-NR) were not significantly different (p = 0.73). The median OS and 12-month OS rate was 26.2 mos (95% CI 21.4-NR) and 89%, respectively, but LPS pts had significantly worse OS (HR 3.5, p = 0.04). Twenty pts experienced at-least one grade (gr) 3 or 4 adverse event (AE); gr 3 or 4 AEs occurred in > 1 pt included hypertension (n = 4); hand-foot-syndrome (HFS) (n = 5), proteinuria (n = 3), febrile neutropenia (n = 3), neutropenia (n = 11, without G-CSF support). Compared to L 18mg/day, pts treated with RP2D were associated with lower gr3/4 HFS and hypertension. There were no sustained grade 3/4 AEs for pts receiving long-term L+E. Conclusions: L + E had shown promising efficacy in advanced LMS and LPS. L at 14mg (vs 18mg) had a better AE profile without compromising activity. Future randomized study to confirm the efficacy of the combination is warranted. Clinical trial information: NCT03526679.
Promising antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).
Authors: Qiu Haibo , Zhou Zhiwei , Zhou Ye , Wan XiangBin , Tao Kaixiong , Li Yong , Wu Xin , Liu Lihui , Chen Zi , Men Lichuang , LIANG ZHIYAN , Lu Ming , Jiang Lixin , Yang Dajun , Xu Rui-hua , Zhai Yifan 
Published: June 2022

11513 Background: GIST is a rare mesenchymal tumor whose management has been transformed by approvals of TKIs. However, treatment resistance is a formidable challenge in managing locally advanced or metastatic GIST. Pts with SDH-deficient GIST are not sensitive to imatinib and other TKIs, are frequently multifocal, and typically have a multinodular architecture. Olverembatinib is a novel, potent, orally active third-generation TKI with promising activity against GIST in multiple preclinical GIST models. Methods: The aim of this phase Ib/II study was to evaluate the safety/tolerability, pharmacokinetics (PK), and efficacy (assessed per RECIST v1.1) of olverembatinib (NCT03594422) in pts with metastatic GIST whose disease was resistant or failed to respond to imatinib or other TKIs. Olverembatinib was administered orally once every other day (QOD) in 28-day repeated cycles. After 3 pts were treated at 20 mg, other pts were randomly allocated in a 1:1:1 ratio to 30, 40, and 50 mg regimens. Results: On the cutoff date of January 30, 2022, 39 pts (median age 52 [range 19-72] years) had received at least 1 dose of olverembatinib. The average (range) treatment period was 5.0 (0.2-35) months. PK analyses indicated an approximately dose-proportional increase in systemic exposure over the dose range of 20 to 50 mg. Thirty-one pts had KIT or PDGFRA mutations, 13 had stable disease for at least 2 cycles as the best response, 8 withdrew early, and 10 had progressive disease before Cycle 3. Very interestingly, 6 of 8 pts with KIT wild-type GIST were confirmed as SDH deficient: 2 pts had partial responses (PRs), 1 patient’s tumor had shrunk by 35.9% and lasted for 16 cycles, and another patient’s tumor had shrunk by 54.2% in the first evaluation. Four pts had stable disease as best response for 2, 6, 14, and 36 cycles. A total of 36 (92.3%) pts experienced treatment-emergent adverse events, most of which were mild or moderate. Ten (25.6%) pts experienced serious adverse events, of which intestinal obstruction attributed to GIST was the most reported. Common treatment-related adverse events (≥ 20%) included increased leukocyte (59.0%) and neutrophil (46.2%) counts, anemia (20.5%), constipation or asthenia (35.9% each), hyperuricemia (25.6%), hypoalbuminemia (23.1%), and elevated AST or ALT (20.5% each). Conclusions: Olverembatinib was well tolerated at doses of up to 50 mg QOD and showed antitumor activity in pts with TKI-resistant SDH-deficient GIST, with 2 PRs in 6 evaluable pts with SDH-deficient GIST and 1 with stable disease for 36 cycles. These promising findings warrant further investigation. Clinical trial information: NCT03594422.
Preliminary results of a phase IB study of olaparib with concomitant radiotherapy in locally advanced/unresectable soft-tissue sarcoma from the French Sarcoma Group.
Authors: Sargos Paul , Sunyach Marie Pierre , Ducassou Anne , Llacer Carmen , Bellera Carine A. , Michot Audrey , Valentin Thibaud , Firmin Nelly , Blay Jean-Yves , Dinart Derek , Italiano Antoine ,   Groupe Sarcome Français
Published: June 2022

11522 Background: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (O) has radiosensitizing properties in several tumor models including sarcomas. We studied safety and activity of O with external beam radiation therapy (EBRT) in patients with locally advanced soft-tissue sarcomas (STS). Methods: This phase I study first assessed four dose levels (DL1:25 mg, DL2:50 mg, DL3:100 mg, DL4:150 mg BID) of O administered in combination with EBRT (59.4 Gy in 33 fractions of 1.8 Gy) using a TITE-CRM design. Next, we recruited 15 additional patients in an expansion cohort to assess the tumor response or the histological response for patients with resectable disease. Tumor response was assessed by investigators according to RECIST 1.1 criteria. Results: A total of 41 patients (17 men, 24 women) were enrolled in both cohorts, of whom 19 (46.3%) underwent post-treatment surgery. We observed 1 DLT at DL1 (n = 5), 1 at DL2 (n = 7), 0 at DL3 (n = 11) and 1 at DL4 (n = 3) during the dose escalation. The recommended dose (RP2D) was 100 mg BID. Most common adverse events related to O and/or EBRT were acute dermatitis (G1/2 63.4% of patients, G3/4 34.1%), edema limbs (G1/2 36.6%), fatigue (G1/2 36.6%), nausea (G1/2 31.7%) and myositis (G1/2 29.3%). Among the 22 patients assessed for tumor response, 3 unconfirmed partial responses, 12 stable diseases, 5 progressive diseases, and 2 non-evaluable responses were recorded as best overall responses. The 6-month non-progression rate in that population was 9.1% [95%CI 1.1%-29.2%]. Six (31.6%) good histological responses and 9 (47.4%) poor responses were observed on the 19 patients who underwent surgery (4 responses non-available). Conclusions: This study shows that the combination of O with EBRT is well tolerated and lead to encouraging downstaging. A little less than half of the population was able to benefit from surgery with positive results in more than 30% of the cases and the rest of the population showed a promising stability of the disease at 6 months. We are currently awaiting a minimum of one year follow-up for the expansion cohort to assess survival. Clinical trial information: NCT02787642.
Outcomes in late-line systemic treatment in GISTs: Does sequence matter?
Authors: Thirasastr Prapassorn , Joseph Cissimol , Araujo Dejka M. , Benjamin Robert S. , Conley Anthony Paul , Livingston J Andrew Andrew , Ludwig Joseph Aloysius , Patel Shreyaskumar , Ratan Ravin , Ravi Vinod , Zarzour Maria Alejandra , Zhou Xiao , Somaiah Neeta 
Published: June 2022

11542 Background: Ripretinib (R) is approved for 4th line treatment of GIST based on superior PFS and OS compared to placebo in a phase 3 study, with RR of 11.8% and PFS of 6.3 months (mo). In addition to having high potency against PDGFRA D842V, avapritinib (A) showed activity in 4th or later lines for KIT mutated patients (pts). The RR was 17% and median duration of response was 10.2 mo from a phase 1 study. It is not known if pts receiving R benefit from A after progression or vice-versa. We retrospectively reviewed outcomes of R and A to determine if sequence affects outcomes. Methods: Pts diagnosed with GISTs and treated with both R and A at UTMDACC from Jan 2016 to Dec 2021 were included. Pts were separated into R-A (RA) or A-R sequence (AR) and outcomes were tabulated. Descriptive statistics were used to summarize characteristics and genetic profiles. Differences between RA and AR groups were calculated using Fisher’s exact. Response was evaluated using RECIST. Kaplan-Meier and Log-rank test were used to estimate and compare PFS and OS between groups. Results: Twenty pts were included in the study; 12 in RA and 8 in AR. Median age was 55 years (R:29.7-76.3). Most pts had small bowel primary (11/20, 55%) followed by stomach (4/20, 20%). All baseline characteristics and mutations were equitably distributed between RA and AR. RR of R was 17% and 14% in RA and AR groups, respectively and RR of A was 33% and 29% in RA and AR, respectively (Table). None of the pts with secondary exon 13 mutations responded to R or A. The drug administration sequence did not affect RR (p = 0.7, 0.62 in R, A). The PFS of the second drug administered, was shortened. PFS did not differ based on type of KIT mutation. Median OS from diagnosis in RA and AR groups were 121.8 (58.2-NR) and 171.3 (73.3-NR) mo, respectively and median OS from start of RA and AR was 43.9 (23.0-NR) and NR (11.5-NR) mo, respectively. Neither difference was statistically significant. Conclusions: Both R and A are efficacious in later lines of treatment, with greater benefit from the agent used first. Although, the combined PFS was numerically higher in AR compared to RA (20.5 vs 15.2 mo), the OS was not different. Currently, R is the only drug approved in the 4th or later lines in KIT-mutated GIST. [Table: see text]
Trabectedin and hypofractionated radiation for high-risk, localized, and metastatic soft tissue sarcoma: A retrospective study.
Authors: Wandrey Narine , Lanning Ryan Michael , Stewart Camille , Elias Anthony D. , McCarter Martin , Wilky Breelyn A. 
Published: June 2022

11564 Background: Soft tissue sarcomas (STSs) are a heterogeneous group of cancers with high unmet need. Trabectedin (T) is an FDA-approved chemotherapy that blocks cell cycling and DNA repair pathways. Combination T and conventional radiation (XRT) in STS nonrandomized phase 1/2 trials demonstrated objective response rates (ORR) of 36-72% in localized and low burden metastatic disease, while pre-treated metastatic STS treated with T alone has an ORR of 10-14%. We hypothesize that the combination of T and hypofractionated radiation (hXRT) will exhibit a tolerable safety profile and improve ORR relative to historical outcomes with T or hXRT alone. Here we report our experience in the treatment of oligometastatic STS with combined T and hXRT. Methods: We reviewed our institutional experience to identify patients treated with T and XRT. We included patients with high risk localized or metastatic STS (majority of patients had metastatic disease at time of treatment). All patients received at least 1 cycle of T and concurrent XRT to at least 1 lesion. ORR and local control rate (LCR) were determined for irradiated lesions by RECIST 1.1. Results: Between 2020 – 2021, 9 STS patients with 21 tumors were treated at the University of Colorado with XRT and concurrent T. The median age was 39.2 (range 26.0 – 64.6) years. 8 patients had metastatic disease at the time of treatment. Treated tumor sites included 1 lung,1 extremity, 2 liver, 2 retroperitoneal, 5 bone, and 10 peritoneal. The following histologic subtypes were included: myxoid liposarcoma (3), uterine leiomyosarcoma (2), non-uterine leiomyosarcoma (1), dedifferentiated liposarcoma (1), undifferentiated pleomorphic sarcoma (1), and synovial sarcoma (1). All metastatic patients were pre-treated with a median of 3 lines of systemic therapy. The median number of T cycles delivered was 5 (range 1 – 20). The median XRT prescription dose was 3000cGy (range 2000cGy – 5000cGy), with 8 patients having received hXRT (5 -10 fractions) and 1 having received conventionally fractionated XRT. 8 patients underwent 1 course of XRT, while 1 received 3 courses in combination with T. All patients had a Karnofsky performance status equal to or greater than 60. After a median follow-up 5.4 months, the LCR of treated lesions was 90.5%. The ORR (CR or PR) was 57.1% and median decrease in tumor diameter at time of maximum response was 52.0%. The median time until maximum response was 3.7 months. 2 patients experienced grade 3 toxicity (LFT elevation) attributable to T, and 2 patients experienced grade 3 toxicity due to XRT. There were no grade 4 or 5 toxicities. Conclusions: T in combination with hXRT appears to be safe and feasible in this patient population. Based on these data, a phase 1/2 prospective clinical trial is being planned in oligometastatic and high risk localized STS. [Table: see text]
Epitheliod hemagioendothelioma (EHE) patient-derived model (PDX): Drug activity assessment and validation of novel biomarkers.
Authors: Stacchiotti Silvia , Zuco Valentina , Frezza Anna Maria , Pasquali Sandro , Tortoreto Monica , Martini Silvia , Barisella Marta , Dagrada Gianpaolo , Huang Paul , Jones Robin Lewis , Casali Paolo G , Leonard Hugh , Gronchi Alessandro , Zaffaroni Nadia 
Published: June 2022

11566 Background: EHE is an ultra-rare sarcoma marked by two specific fusions, WWTR1-CAMTA1 (̃90%) and YAP1-TFE3 (̃10%). The clinical course of EHE ranges from indolent to highly aggressive, often associated with systemic paraneoplastic symptoms. Molecular predictors of clinical outcome are unknown. While surgery is the mainstay of treatment in the localized setting, management of advanced disease is challenging due to the rarity and poor sensitivity to conventional chemotherapy. This hampers the conduct of large prospective clinical trials. We report herein the first available EHE PDX (developed at the Istituto Nazionale Tumori, Milan, Italy) (INT), to assess the activity of old and new anticancer agents in EHE and inform future clinical studies. We also report on the preliminary results of a prospective observational study, ongoing in collaboration with The EHE Rare Cancer Charity (UK) and The EHE Foundation (US) aimed at identifying prognostic factors. Methods: A PDX of EHE in SCID mice was generated at INT from a patient (pt) suffering with the aggressive clinical variant, presenting with systemic symptoms. The PDX fully reproduces the originating clinical tumor in terms of morphology, biology ( WWTR1- CAMTA1 positive), overall transcriptomic profile. 2D (monolayer) and 3D (sferoids) cell cultures were established following PDX disaggregation. We have started assessing the comparative activity of currently available drugs (doxorubicin, sirolimus), while the efficacy of novel agents is undergoing. In parallel, we analyzed the presence of a selection of inflammatory cytokines in prospectively collected blood samples from EHE pts who entered an international observational study and we looked at their presence and modulation in the PDX model. Results: PDX experiments showed almost negligible activity of doxorubicin while sirolimus induced an 80% tumor volume inhibition. Biochemical analysis in tumors explanted from sirolimus-treated mice confirmed the down-regulation of mTOR downstream signaling. Among all cytokines, Growth and Differentiation Factor-15 (GDF-15) was found significantly over-expressed in serum of EHE pts (n = 23), particularly those with the most aggressive clinical variant, compared to healthy subjects (n = 23; p< 0.01). Consistently, EHE PDX and cell culture were found to release in the blood/culture medium GDF-15. Sirolimus was found to down-regulate GDF-15 release in both in vivo and in vitro EHE models. Conclusions: Our preliminary results indicate that this EHE PDX model is suitable i) for comparatively assessing the activity of anticancer drugs, and ii) for identifying and pre-clinically validating novel biomarkers. The role of GDF-15 in EHE progression deserves further investigation.