bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout among early-career medical oncologists: A single-institution experience.
Authors: Singh Anmol , Xiao Lianchun , O'Brien Barbara Jane , Flowers Christopher , Bruera Eduardo , Morris Van K. , Shah Amishi Yogesh
Published: June 2022

11015

Background: Burnout is a psychological syndrome defined by the Maslach Burnout Inventory (MBI) as emotional exhaustion, depersonalization, and a low sense of personal accomplishment. Risk of job-related burnout for early-career medical oncologists can significantly impact career longevity and health outcomes for providers and patients alike. Because little is known about burnout specific to early-career academic oncologists, we sought to characterize the prevalence of burnout and associated factors among Assistant Professors at MD Anderson Cancer Center (MDACC). Methods: For this IRB-approved retrospective study, an electronic survey was developed for Assistant Professors in medical oncology at MDACC. Participants were all involved directly in patient care with at least some clinical effort. Our survey included nine questions validated in the MBI addressing equally the 3 aforementioned domains of burnout. An additional 31 questions were formulated to assess personal and professional factors that may contribute to burnout at our institution (clinical workload, research expectations, communication, COVID, and home-life). Each question was scored on a scale of 1 to 5, with higher scores correlating to higher levels of burnout. Descriptive statistics were used to describe the prevalence of burnout, and logistic regression analyses were performed to identify characteristics associated with burnout. Results: Among 70 (of 86 total) Assistant Professors who responded, mean duration on faculty was 3.1 years (standard deviation +/-1.8). Mean clinical effort was 67% (range, 19-95). Gender identifications were 44% female, 54% male, and 2% non-binary. 54% of respondents reported symptoms of burnout already, including 21% endorsing severe burnout. Severe burnout was more common for solid tumor providers than liquid tumor providers (55% vs 13%, p =.03). Using the MBI, severe emotional exhaustion (25%) was more prevalent (p <.0001) than depersonalization (6%) or lack of personal accomplishment (17%). Sentiments of being “emotionally drained” (20%), fatigue to face another day on the job” (37%), and “becoming more callous” (30%) were especially concerning among early-career faculty. Emotional exhaustion was associated with a feeling of less autonomy over personal decision making (p =.03) and female gender (p =.04). Conclusions: Burnout exists with high prevalence among early-career medical oncologists in this single-institution analysis. Emotional exhaustion was the specific manifestation of burnout in this population. Further validation of these data nationwide is anticipated. Interventions focusing on reducing emotional exhaustion are under development to reduce medical oncology-specific burnout in an academic setting for faculty retention and for deliverance of optimal care to patients with cancer.
Medical student readiness to treat LGBTQ patients.
Authors: Schabath Matthew B. , Karpel Hannah C , Sampson Amani , Charifson Mia , Fein Lydia , Murphy Devin , Sutter Megan , Tamargo Christina , Quinn Gwendolyn
Published: June 2022

11030

Background: The lesbian, gay, bisexual, transgender and queer (LGBTQ) community experiences cancer health disparities. It is thus imperative that medical trainees receive training in the care of LGBTQ populations. Identifying gaps in trainees’ knowledge and comfort in providing care for this population is important in preparing future physicians. Methods: A Likert-scale survey of US medical students at three institutions assessed attitudes, comfort and knowledge in providing care for LGBTQ patients. Results were quantified with descriptive and stratified analyses. Exploratory factor analysis found four factors in which attitude summary measure (ASM) scores were calculated; lower values indicate more agreeability with given attitude items. Total knowledge scores were calculated with higher values indicating greater knowledge. Results: Of 300 medical students who completed the survey, the majority were female (55.7%), white (54.7%), and heterosexual (64.3%). The majority of students felt comfortable (strongly agree/agree) participating in the care of patients who identify as lesbian (94.3%), gay (96.0%), and bisexual (96.3%); this percentage dropped to 82.3% for non-binary and 71.3% for transgender patients. Only 27.0% of students reported confidence in their knowledge of health needs of transgender patients. LGBTQ self-identification, percent of core rotations completed, and having LGBTQ friends/family were significantly associated with various ASM subscales (Table 1). Knowledge questions had high percentages of “neutral” responses, and students who identified as LGBTQ had significantly higher total knowledge scores. Conclusions: Overall, medical students feel comfortable and willing to provide care for LGBTQ patients. However, as in our prior study in oncologists, there is limited knowledge about specific LGBTQ health and cancer needs. More education and training in the needs of transgender and non-binary patients is indicated. [Table: see text]
A longitudinal study assessing the impact of ongoing COVID-19 pandemic among hematology-oncology trainees.
Authors: Shikdar Sufana , Saleem Rabia , Alcid Joel , Mukherjee Sarbajit , Hassan Ayesha , Keshava Vinay E. , Razaq Humza , Aljumaily Raid
Published: June 2022

11033

Background: Hematology-Oncology (HO) trainees faced significant challenges due to the COVID-19 pandemic highlighted by a previous survey (Durani, Urshila, et al. "Impact of COVID-19 on Hematology-Oncology Trainees: A Quantitative and Qualitative Assessment." JCO Oncology Practice (2021): OP-21). Despite the positive impact of effective vaccines, the pandemic is still ongoing; thus, the challenges remain. Our aim is to evaluate how well the trainees have adapted to changes in their clinical training environment after the early phase of the COVID-19 pandemic. Methods: A cross-sectional internet-based survey (Shih, Grace, et al. "The impact of the COVID‐19 pandemic on the education and wellness of US Pediatric Anesthesiology Fellows." Pediatric Anesthesia 31.3 (2021): 268-274) from December 10, 2021, to January 10, 2022, was obtained from the trainees enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited HO fellowship programs in the United States in their fourth (PGY4), fifth (PGY5), and sixth (PGY6) postgraduate year. Results: The survey was completed by 102 trainees. Demographics of the participants are reported in Table. Interestingly, 51% reported an impact of COVD-19 on their employment plans, primarily due to the inability to interview in person (24%, n=23). Trainees experienced several stressors due to the pandemic, including fear of getting sick from a patient (71%) or a coworker (66%). Approximately 27% (n=26) experienced mental health issues requiring additional care. Less than one-third of the trainees were concerned about clinical expertise and procedural skills. Trainees also felt that the change of conference to virtual format impacted their learning activities compared to in-person education (66%, n=64). Most trainees (52%, n=53) reported limited involvement in COVID-related research and journal club education. Most had access to socialization (59%, n=60), virtual office hours (70%, n=72), and telehealth visits (83%, n=85). Female trainees (18%) were more likely to seek mental health care than the male trainees (7.8%) (P=.02). Female trainees (33%) also reported facing more challenges in their employment plans compared to males (16%) (P=.003). Conclusions: Our study highlights the challenges experienced by hematology-oncology trainees with the ongoing COVID-19 pandemic and reveals the gender gap related to employment plans and seeking mental health care. [Table: see text]
Gender disparity in authorship of clinical trials leading to cancer drug approvals between 2008 and 2018: The glass ceiling of academic oncology.
Authors: Chapman Lynne O. , Loree Jonathan M. , Anand Seerat , Mendis Shehara Ramyalini , McNeill Lorna H , Raghav Kanwal Pratap Singh , Varadhachary Gauri Rajani
Published: June 2022

11048

Background: Authorship, expressly premier positions (first, corresponding, or senior author), in peer reviewed journals is widely acknowledged as scientific credit in academia. Yet, gender inequities and biases pervade this facet of the scientific ecosystem. We reviewed the authorship of pivotal FDA trials that established the standards of care in oncology over the past decade with the goal of defining the magnitude of gender disparity in the most influential literature of the field in recent years. Methods: We collected and assessed data from the primary publication of 231 trials that enabled FDA drug approvals in hematology and oncology from July 2008 to June 2018. Author gender was assigned from listed names using statistical probability and confirmed using institutional websites and online databases (genderchecker database, biographical paragraphs, and social media). Authors where gender was not clearly identified (1.23%) were excluded. To account for equal authorship contribution, we included co-authors as distinct data points, and credit was given to reports for any women in premier authorship positions (first, corresponding, or senior author) to avoid overestimating disparity. Descriptive statistics were used, and 95% confidence intervals (95%CI) were reported using modified Wald method. Proportions were compared using Fisher-exact and Chi-squared test. Unadjusted P values of < 0.05 were considered significant. Results: A total of 4664 (98.8%) authors were included in this analysis across 227 publications. Of these, 1287 (27.6%) were female with a median of 25.9% female authorship in total per trial. Female authorship was significantly higher for non-randomized (30.4% v 26.5% for randomized, P = 0.007) and phase 1/2 trials (29.9% v 26.3% for phase 3, P = 0.009) and varied with trial size (P < 0.001), with the proportion greater in trials with ≤100 patients versus those with > 500 patients. Female authorship in fields of breast and gynecological oncology was higher (41.3%) than other cancers (26.0%, P < 0.001). Women were proportionally less likely to hold premier (9.2% v 18.2%, OR 0.46, 95%CI: 0.4 – 0.6, P < 0.001), first (3.2% v 6.3%, OR 0.49, 95%CI: 0.3 – 0.7, P < 0.001), senior (3.3% v 6.0%, OR 0.54, 95%CI: 0.4 – 0.8, P = 0.002) and corresponding (2.5% v 5.8%, OR 0.42, 95%CI 0.3 – 0.6, P < 0.001) authorship but not second author role (4.1% v 5.1%, OR 0.80, 95%CI 0.6 – 1.1, P = 0.17). Conclusions: The under-representation of women in premier authorship positions in pivotal clinical trials, demonstrated in our study, serves as a barometer of a biased academic infrastructure, amplifying existing calls to address barriers that limit the full inclusion of women in oncology.
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.
Correlation of psychological distress with quality of life and efficacy of immune checkpoint inhibitors in patients with newly diagnosed stage IIIB-IV NSCLC.
Authors: Wu Fang , Hu Chunhong , Li Yizheng , Zeng Yue , Liu Junqi , Liu Xiaohan , Ma Fang , Qiu Zhenhua , Deng Chao
Published: June 2022

12001

Background: Psychological distress is common among cancer patients and leads to activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) and continuous production of distress hormones, which may contribute to a highly immunosuppressive tumor microenvironment (TME). Meanwhile, preclinical studies have shown that psychological distress could undermine cancer therapies. Therefore, we investigate the prevalence of psychological distress in non-small-cell lung cancer (NSCLC) patients, identify its impact on quality of life (QoL) and efficacy of immune checkpoint inhibitors (ICIs), and explore the possible neuro-endocrinological mechanisms. Methods: Patients with newly diagnosed stage ⅢB-Ⅳ NSCLC received ICIs as first-line treatment were included. The assessments of psychological distress including depression and anxiety symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The QoL was measured by Short Form Health Survey 36 (SF-36). Stress hormones including serum cortisol, adrenocorticotropic hormone (ACTH), plasma epinephrine (Epi), and norepinephrine (NE) were determined by ELISA kit before treatment. Objective response rates (ORR) and Median progression-free (PFS) were estimated using the Chi-square test, Kaplan-Meier, and Cox regression method. Results: 77 NSCLC patients with a mean age of 60.9 years were enrolled. Stage distribution included 50 (64.9%) stage ⅢB/C and 27 (35.1%) stage Ⅳ. 44(57.1%) patients were present psychological distress. Psychological distress was associated with poorer QoL (P<0.001). The median follow-up time was 16.2 months. Compared with non-psychological distress patients, psychological distress patients had a significant lower ORR (35.9% vs 63.64%; P=0.033) and shorter PFS (median 12.63 vs 14.60 months; 95% CI: 0.36 to 1.98; P=0.026). Moreover, psychological distress was the only independent predictor for PFS (HR:2.71, 95%CI: 1.06～6.90; P=0.037) in multivariate Cox regression analyses. The patients with psychological distress had higher levels of serum cortisol ( P=0.040) and plasma Epi ( P=0.023). Additionally, the serum cortisol ( P=0.043) and plasma Epi ( P=0.025) concentrations were associated with inferior ICIs response. Conclusions: Psychological distress is common within stage ⅢB-Ⅳ NSCLC patients. Patients with psychological distress are associated with worse QoL and inferior outcomes to ICIs and discover the potential mechanisms of neuro-endocrinological hormones in resistance to ICIs therapy.
Open-labeled placebo for the treatment of cancer-related-fatigue in patients with advanced cancer: Results of a randomized controlled trial.
Authors: Yennu Sriram , Azhar Ahsan , Lu Zhanni , Rodriguez Ashley , Arechiga Adrienne , Guerra-Sanchez Maria , Stanton Penny A , Andersen Clark , Urbauer Diana L. , Bruera Eduardo
Published: June 2022

12006

Background: Despite the high frequency of cancer related fatigue (CRF) in patients with advanced cancer (PAdC), there are no effective pharmacological treatments. Our group previously found that the placebo response was 56% among PAdC participating in CRF trials. There are no clinical trials using open label placebo for CRF in PAdC. The purpose of this study was to determine the effects of open labeled placebo (OLP) compared to waitlist control (WLC) in reducing CRF in PAdC using Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-F). Methods: In this randomized controlled trial, PAdC with fatigue ≥ 4/10 on ESAS were randomized to OLP one tablet twice a day or WLC for seven days (primary end point). After week 1 in patients of both arms received placebo for 3 weeks. Changes in FACIT-F from baseline to Day 8 (primary outcome), and changes after 21 days of placebo in both arms were assessed. Secondary outcomes included quality of life (QOL)[FACT-G], fatigue dimensions(MFSI-SF), depression(CES-D), and Fatigue cluster(ESAS fatigue, pain, and depression). Results: 82/90(91%) patients were evaluable. The adherence to placebo [mean%(SD)], was 93.6(18.6), and 88.1(20.2) at Day 8 and Day 29 respectively in OLP arm, and 89.9 (73) at Day 29 in WLC arm. The mean(SD) FACIT-F change at day 8 was 6.6 (7.6) after OLP, 2.1 (9.4) after WLC (p = 0.016). On days 15 and 29, when all patients received OLP, there was significant improvement of CRF but not difference between arms. FACT-G Total Score, FACT-G EWB, ESAS Fatigue, and Fatigue cluster score, all showed significant evidence of reduced CRF in the OLP arm on Day 8 of the study (p = 0.002, 0.030, 0.029, and 0.044, respectively). There was no significant difference in adverse events between the two groups. Conclusions: Open labeled placebo was efficacious in reducing CRF, fatigue cluster, and QOL in fatigued advanced cancer patients at the end of one week. The improvement in fatigue was maintained for 4 weeks. Further studies of this intervention are justified. Clinical trial information: NCT03927885.
Strategies for implementing an ePRO-based symptom management program (eSyM) across six cancer centers.
Authors: Hassett Michael J. , Cronin Christine , McCleary Nadine Jackson , Bian Jessica J , Wong Sandra L. , Hazard-Jenkins Hannah W. , Dias Samira , Johnson Julie , Schrag Deborah , Dizon Don S. , Osarogiagbon Raymond U. ,   eSyM Project Managers Author Group
Published: June 2022

12017

Background: Electronic patient-reported outcome (ePRO)-based symptom management can improve cancer care outcomes. However, implementation is challenging as it requires 1) tremendous technical resources to integrate ePROs into the electronic health record (EHR), 2) substantial buy-in from clinicians and patients, 3) between visit symptom management, and 4) institutional investment to support engagement. Methods: The SIMPRO Consortium developed and deployed eSyM, an EHR-integrated ePRO-based symptom management program for medical oncology and surgery patients, at 6 cancer centers between September 2019-March 2022. Site teams document new and changes to implementation strategies monthly using REDCap (data collection is ongoing). Strategies are itemized using the Expert Recommendations for Implementation Change (ERIC) list and mapped to the Consolidated Framework for Implementation Research (CFIR) list of barriers. The SIMPRO Coordinating Center (Dana-Farber) reviews all ERIC-CFIR classifications for consistency. Results: To date, 162 distinct strategies have been documented. On average, sites have implemented 23 strategies, 5 preparing for go-live and 18 remaining active beyond go-live. Preparation of clinical staff, training, and routine program evaluation are consistent high impact strategies. Other adaptive strategies have varied across sites, including various approaches to patient and provider engagement. Foundational strategies have been deployed by the coordinating center to support the multi-center initiative. Conclusions: Methodical deployment using theory-based implementation strategies may foster adoption of novel health care delivery systems by patients, clinicians, and institutions. Attention to the specific high-value strategies identified by the SIMPRO Consortium could support similar ePRO deployment at other institutions. [Table: see text]
Vitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221.
Authors: Chen Ciao-Sin Chelsea , Zirpoli Gary , McCann Susan , Barlow William E. , Budd George Thomas , Pusztai Lajos , Hortobagyi Gabriel N. , Godwin Andrew K. , Thompson Alastair Mark , Ambrosone Christine B. , Stringer Kathleen A , Hertz Daniel Louis
Published: June 2022

12023

Background: Peripheral neuropathy (PN) is a treatment-limiting toxicity of paclitaxel. Black patients have higher rates of PN and vitamin D insufficiency, and our prior work suggests vitamin D insufficiency increases risk of paclitaxel-induced PN. The objective of this study was to validate that patients with vitamin D insufficiency have higher risk of paclitaxel-induced PN and investigate whether this explains racial disparities in PN risk. Methods: This retrospective validation study was conducted in the phase III SWOG 0221 (NCT00070564) trial comparing paclitaxel-containing chemotherapy regimens for early-stage breast cancer. Pre-treatment 25-hydroxy-vitamin D was quantified in cryopreserved serum. Males and patients who received less than a third of the paclitaxel treatment were excluded. The association between vitamin D insufficiency (≤20 ng/mL) and grade 3+ sensory PN was tested via logistic regression and then adjusted for self-reported race, age, paclitaxel schedule (QW vs Q2W), and body mass index. Results: Of the 1,116 female patients in the analysis, 169 (15.1%) experienced PN and 376 (33.7%) had vitamin D insufficiency. Vitamin D insufficiency was associated with higher PN risk (19.4% vs 13.0%, OR = 1.62, p = 0.005, Data Table). The association was borderline significant (OR = 1.44, p = 0.056) after adjustment for black race (OR = 2.41, p = 0.001), paclitaxel schedule (OR = 2.22, p < 0.001), and age (OR = 1.03, p = 0.005). Compared with white patients (n = 943), black patients (n = 99) had more prevalent vitamin D insufficiency (77.8% vs 28.6%, OR = 8.72, p < 0.001) and increased PN risk (29.3% vs 13.5%, OR = 2.66, p < 0.001); adjusting for vitamin D insufficiency decreased but did not eliminate the higher PN risk in black patients (OR = 2.23, p = 0.002). Conclusions: Vitamin D insufficiency increases risk of paclitaxel-induced PN and partially explains the higher risk of PN in black patients. Prospective trials are needed to test whether vitamin D supplementation lessens PN and reduces disparities in treatment outcomes. [Table: see text]
The impact of primary palliative care on advance care planning in advanced cancer.
Authors: Cohen Michael , Althouse Andrew , Chu Edward , Resick Judith , Rosenzweig Margaret Q. , Smith Kenneth , White Douglas B. , Schenker Yael
Published: June 2022

12030

Background: Palliative care specialists are experts in conducting advance care planning (ACP), but are a limited resource. We sought to determine the impact of a nurse-led primary palliative care intervention on ACP completion among patients with advanced cancer. Methods: We performed a secondary analysis of a cluster randomized controlled trial looking at the impact of nurse-based primary palliative care at community cancer centers. In the parent trial, patients with advanced cancer received either monthly primary palliative care visits with trained nurses within their cancer center or usual care. Nurses in the intervention arm received special training in addressing symptom management and ACP. ACP uptake was assessed at enrollment and 3 months later via validated questionnaire in the forms of an end-of-life conversation (EOLC) with one’s oncologist or completion of an advance directive (AD). The present analyses were restricted to patients without ACP at baseline. Multivariable logistic regression tested differences in ACP uptake by treatment arm when adjusting for age, religious importance, education, time with current oncologist, and ECOG. Results: Of 672 patients enrolled, 182/336 in the intervention arm and 196/336 in usual care lacked an EOLC at baseline and completed three-month assessments. Of those, 82/182 (45.1%) in the intervention arm and 29/196 (14.8%) in the usual care arm reported having an EOLC at three months (Table). Similarly, 111/336 in the intervention arm and 105/336 in usual care lacked an AD at baseline and completed the three-month assessments. Of those, 48/111 (43.2%) in the intervention arm and 19/105 (18.1%) in usual care completed an AD over the study period (Table). For both types of ACP, the treatment effect suggested increased uptake of new ACP in the intervention arm after controlling for variables known to be associated with ACP (Table) Conclusions: Nurse-led primary palliative care increased the uptake of ACP among patients with advanced cancer. Training oncology nurses embedded within community cancer centers may represent a feasible mechanism to improve access to primary palliative care and uptake of advance care planning. Clinical trial information: NCT02712229. [Table: see text]