bluuebunny/crossref_metadata_2025 huggingface dataset:
Change in cardiac function with CPX-351 in relapsed pediatric AML: A Children’s Oncology Group (COG) report from AAML1421.
Authors: Leger Kasey J. , Absalon Michael , Demissei Biniyam G , Gerbing Robert B , Alonzo Todd Allen , Hirsch Betsy A , Pollard Jessica Anne , Razzouk Bassem I. , Kolb E. Anders , Aplenc Richard , Ky Bonnie , Cooper Todd Michael
Published: May 2020

10532

Background: Anthracyclines (AC) are highly effective in treating acute myeloid leukemia (AML), but limited by cardiotoxicity (CTX). CPX-351, a liposomal preparation of daunorubicin (DNR) and cytarabine, may provide therapeutic benefit with less CTX. We evaluated acute changes in cardiovascular (CV) function and biomarkers after 1 cycle of CPX-351 in children with relapsed AML within the phase 1/2 study, AAML1421. Methods: Patients (pts) received 135 units/m2/dose of CPX-351 on days 1, 3, and 5. Echocardiograms were centrally quantified at baseline (BL) and day 29 (end of cycle (EOC)). High sensitivity troponin (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at BL and days 5, 8, 15, 22, and 29. Differences between BL and post-CPX-351 echo/biomarker measurements were analyzed using pre-specified Wilcoxon signed rank tests. The relationship between EOC ejection fraction (EF) and clinical variables was assessed using repeated measures linear regression. Results: In 32 included pts, the median AC exposure prior to study entry was 337 mg/m2 DNR equivalents. At baseline, markers of CV function and stress were abnormal (Table). Over 1 cycle, there was a statistically significant decrease in EF and circumferential strain (Table). NT-proBNP and cTnT did not increase significantly over time. In multivariable analysis, only increasing body surface area was significantly associated with lower EOC EF (b:-5.9, 95% CI -10.8,-0.9). Cancer therapy–related cardiac dysfunction, defined as ≥10% decline in EF to < 50%, occurred in 6/32 pts at EOC. Conclusions: In this single arm study of AC pre-treated children, baseline abnormalities in CV function were common. CPX-351 was associated with a statistically significant decline in CV function without a rise in cardiac biomarkers. Absent a comparator population, it is not known how these cardiac trends compare to non-liposomal AC or non-AC salvage regimens. The COG AAML1831 trial will determine if CPX-351 offers cardioprotection compared to standard AC in pts with de novo AML. Clinical trial information: NCT02642965. [Table: see text]
Risk factors in the HR-NBL-1/SIOPEN study in patients receiving dinutuximab beta (DB) based immunotherapy.
Authors: Ladenstein Ruth Lydia , Poetschger Ulrike , Valteau-Couanet Dominique , Gray Juliet , Luksch Roberto , Balwierz Walentyna , Castel Victoria , Ash Shifra , Beck Popovic Maja , Laureys Genevieve , Chan Godfrey Chi-Fung , Ruud Ellen , Vettenranta Kim , Owens Cormac , Schroeder Henrik , Ambros Peter F , Sarnacki Sabine , Boterberg Tom , Lode Holger N.
Published: May 2020

10536

Background: We previously developed a risk factor model in HR-NBL1/SIOPEN patients treated without DB including age, LDH and metastatic site index (MSI). We tested if this score (Morgenstern, PBC 2018) would provide meaningful information in DB treated HR-NBL1/SIOPEN patients. Methods: High-risk patients (stage 4 ≥1yr.; stage 4 < 1yr. with MYCN amplification (MNA); stage 2, 3, 0-21y with MNA) received intensive induction, surgery, high dose therapy (HDT) and local radiotherapy (21Gy). Patients with a ≤9 months intervall till HDT/SCT, ≥ partial response prior and no progression received up to 5 cycles of 100mg/m2 DB: as short-term (STI: 5 days) or long-term infusion (LTI: 10 days ) ± 6 (STI) or 3 (LTI) x 106 IU/m2 subcutaneous interleukin 2 (scIL2 over 2 x 5 days) followed by 2 weeks of 160mg/m2 oral isotretinoin. Results: DB was used in 1018 patients [512 males; 89% Stage, 1% Stage 4s, 10% loc. MNA; 2.8 yrs median age at diagnosis] in 18 countries. STI was used in 61% patients, LTI in 39% and DB without scIL2 in 62% patients. 2-yrs. event-free (EFS)/overall survival (OS) was 0.65±0.02/0.78±0.01 and 5-yrs. EFS/OS of 0.56±0.02/0.63±0.02. 891/1018 patients were evaluable for risk factor analysis. EFS multivariate analysis included age, MSI, LDH ≥1250U/L, HDT typ, response prior DB, DB schedule and use of scIL2: only age > 1.5yrs.(p = 0.002) and MSI > 1 (p = 0.002) had independent prognostic prediction. If restricted to stage 4 only, LDH ≥1250U/L was also an independent factor (p = 0.049). Points were allocated in proportion to the log-cumulative hazard ratio (cHR): cHR for LDH > 1250U/L was 1.33 (score of 1), cHR for age > 5 years and metastatic site involvement (MSI) > 1 were 1.79 and 1.86 (scores of 2). Using the score (0 to 5) relevant risk groups can be identified: 5-yrs. EFS/OS for scores 0&1 are 0.80±0.06&0.77±0.04, score 2/3 are 0.58±0.03&0.57±0.04 and for scores 4/5 are 0.50±0.06&0.43±0.08. Conclusions: The score adds value in DB treatment groups as it differentiates prognostic subgroups facilitating decision making for future DB add on treatments. Clinical trial information: NCT01704716.
Lung cancer as a subsequent neoplasm: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Ghosh Taumoha , Chen Yan , Dietz Andrew C , Armstrong Gregory T. , Howell Rebecca M. , Mulrooney Daniel A. , Turcotte Lucie Marie , Yuan Yan , Yasui Yutaka , Neglia Joseph Philip
Published: May 2020

10551

Background: Lung cancer has been reported as a subsequent neoplasm (SN) in childhood cancer survivors. We aimed to assess the prevalence of and risk factors for lung cancer in the CCSS. Methods: Among 25,654 five-year survivors participating in the CCSS, lung cancer was self-reported and then confirmed by pathologic record review. Cancer treatment exposures were evaluated including chemotherapy and chest radiation by field size (none, small, large) and in a dose group (0-10 Gy, 10-30 Gy, 30-40 Gy, and > 40 Gy). Standardized incidence ratios (SIR) were calculated using rates from the Surveillance, Epidemiology, and End Results program. Hazard ratios (HR) were estimated for demographic and treatment variables using Cox proportional-hazards models. Results: Forty-two survivors developed subsequent malignant lung cancer (SIR 4.0, 95% CI 2.9-5.4), including 25 carcinomas, 7 mesotheliomas and 10 others. Two additional benign neoplasms were also identified. The cumulative incidence of lung SNs was 0.18% at 30 years (95% CI 0.10-0.25). Median time from primary diagnosis was 28 years (range 11-46); median age at diagnosis was 45 years of age (range 15-65). A multivariable model, including all covariates with a p-value < 0.2 in univariate analysis, showed significant associations between lung cancer and older age at diagnosis (HR 10.5, 95% CI 1.4-76.4, for 15-21 years vs. 0-4 years), as well as with primary diagnoses (relative to leukemia, HR 8.7, 95% CI 1.1-66.0, for Hodgkin lymphoma; HR 20.7, 95% CI 1.3-331.0 for neuroblastoma; and HR 21.4, 95% CI 2.3-202.7, for bone cancer). In a treatment model, maximum chest radiation dose (HR 4.1, 95% CI 1.4-11.7, for 30-40 Gy; and HR 8.1, 95% CI 3.0-22.2, for > 40 Gy, relative to 0-10Gy), but not sex, smoking status, or chemotherapy exposures, was associated with lung cancer. Notably, six survivors who developed lung cancer received no radiation and of these, five had a primary bone cancer. At the end of follow-up, 65.9% of survivors with lung cancer were deceased vs. 14.1% of survivors without lung cancer ( p < 0.001). Conclusions: Survivors of childhood cancer are at increased risk for developing lung cancer associated with exposure to high doses of chest radiotherapy. To our knowledge, this is the first study to describe associations with neuroblastoma and bone cancer. Future studies to understand additional treatment-related risk factors beyond chest radiotherapy dose are needed.
The efficacy of first-line chemotherapy in endocrine-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2- negative (HER2-) metastatic breast cancer (MBC).
Authors: Chainitikun Sudpreeda , Long James , Rodriguez-Bautista Ruben , Iwase Toshiaki , Tripathy Debu , Fujii Takeo , Ueno Naoto T.
Published: May 2020

1056

Background: Combinations of endocrine therapy (ET) and targeted therapy (CDK4/6 or mTOR inhibitors) are standard of care for HR+/HER2- MBC. When ET is not effective, chemotherapy is commonly used. However, clinical outcomes of chemotherapy in the endocrine-resistant setting are limited. We hypothesized that clinicopathological baseline and prior ET factors determine chemotherapy’s efficacy. We sought to identify predictive factors and the compare efficacies of chemotherapy agents in endocrine-resistant MBC. Methods: We conducted a retrospective study of patients with HR+/HER2- MBC who received chemotherapy after progression on ET with or without targeted therapy at MD Anderson Cancer Center from 1999-2017. We collected baseline clinicopathological and all treatment data. The primary endpoint was time to treatment failure (TTF) of first-line chemotherapy for MBC. We performed univariate and multivariate analyses using the Cox proportional hazard model. Kaplan-Meier methods were used to analyze TTF. Results: In the 1,258 patients analyzed, the mean age was 55.3 years (range 21-91). Forty-five patients (3.6%) had inflammatory breast cancer (IBC). Three hundred ninety patients (31%) received previous targeted therapy: 264 with CDK4/6 inhibitor, 205 with mTOR inhibitor, and 79 with both. The most frequent chemotherapy agents were capecitabine (48.9%) and taxanes (paclitaxel, nab-paclitaxel, or docetaxel; 28.6%). After adjustment for all factors in a multivariate model, IBC and prior exposure to a CDK4/6 inhibitor were significantly associated with shorter TTF. Previous treatment with a CDK4/6 inhibitor had the strongest negative effect on chemotherapy TTF regardless of ET duration (adjusted hazard ratio [HR] 1.84; 95%CI 1.49-2.27; p < 0.001). Capecitabine had significantly longer median TTF than taxanes regardless of whether patients had prior exposure to taxanes in (neo)adjuvant setting (6.1 vs 4.9 months; HR 0.64; 95%CI 0.55-0.75; p < 0.001). Conversely, the median TTF for taxanes was shorter in patients who received prior (neo)adjuvant taxanes than in those who did not (4.5 vs 5.1 months). Conclusions: Previous exposure to CDK4/6 inhibitor had a negative predictive effect for the efficacy of chemotherapy. Capecitabine had the best efficacy against endocrine-resistant breast cancer.
Prevalence and characterization of dermatologic adverse events related to alpelisib (BYL719) in breast cancer patients.
Authors: Barrios M.S Dulce M. , Wang Diana G. , Blinder Victoria Susana , Bromberg Jacqueline , Drullinsky Pamela , Funt Samuel Aaron , Jhaveri Komal L. , Lake Diana , Lyons Tomas , Modi Shanu , Razavi Pedram , Sidel Michelle , Traina Tiffany A. , Vahdat Linda T. , Lacouture Mario E.
Published: May 2020

1063

Background: Rash develops in approximately 50% of breast cancer patients receiving alpelisib, often requiring dose modifications. Herein, we describe the characteristics of alpelisib-related dermatologic adverse events (dAEs). Methods: A single center retrospective analysis was conducted via review of electronic medical records. We collected clinical, laboratory and management data relevant to patients treated with alpelisib for advanced breast cancer under four different randomized clinical trials or post approval by regulatory agencies from 6/1/2013 to 7/31/2019. Type and severity of dAEs was recorded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Results: A total of 102 patients (mean age 56 years, range 27-83) receiving alpelisib from 200 to 350 mg daily, most frequently in combination with endocrine therapy (79, 77.5%) were included. We identified 41 (40.2%) patients with all-grade rash [CTCAE grade 1/2 = 22 (21.6%); CTCAE grade 3 = 19, (18.6%)] distributed primarily along the trunk (18, 78%) and developing, on average, within 12.8 +/- 1.5 days of treatment initiation (n = 38). Mean duration of rash was 7.1 +/- 3.8 days; and no grade 4 dAEs were observed. Of 29 patients with documented morphology of alpelisib-related dAEs, the majority (26, 89.7%) had maculopapular rash. Thirteen (68%) of 19 patients with any-grade rash and report of any associated symptoms had pruritus (7, 36%) or burning pain (6, 32%). All-grade dAEs correlated with an increase in serum eosinophils from 2.7% to 4.4% (p < 0.05), and prophylaxis with non-sedating antihistamines (n = 43) was correlated with a reduction of grade 1/2 rash onset (OR 0.39, p = 0.09). Sixteen (84.2%) of 19 patients with grade 3 dAEs had interruption of alpelisib, followed by management with antihistamines, topical and/or systemic corticosteroids. We did not observe rash recurrence in 12 (75%) of these 16 patients who re-initiated therapy; and the majority (9, 56.3%) were re-challenged without a dose reduction. Conclusions: Pruritus and increased blood eosinophils occur with maculopapular rash within the first two weeks of initiating alpelisib and persists for approximately seven days. To reduce onset of grade 1/2 rash, non-sedating antihistamines (i.e. cetirizine) are recommended during the first eight weeks. While grade 3 rash leads to interruption of alpelisib, dermatologic improvement is evident with systemic corticosteroids; and most patients can resume therapy at a maintained or reduced dose upon re-challenge.
Combination of fulvestrant and chemotherapy in ESR1 Y537S mutant breast cancer cells and potential synergy mechanism related to p53 wildtype.
Authors: Ma Wen , Hermida-Prado Francisco , Guarducci Cristina , Feit Avery , Nardone Agostina , Cohen Gabriella , Pan Wenting , Wei Hongliang , Li Nanlin , Brown Myles , Jeseslsohn Rinath
Published: May 2020

1065

Background: The acquisition of ligand-independent ESR1 mutations during endocrine therapy in metastatic ER+ breast cancer is a common mechanism of resistance to endocrine treatment, particularly aromatase inhibitors, and found in more than 30% of patients with metastatic ER+ breast cancer. Our recent work showed that the ER mutations confer resistance to currently available endocrine treatments while promoting an aberrant ER transcriptional activity that drives metastases. These results underscore the importance of targeting the ESR1 mutations even after the development of endocrine resistance. We hypothesized that during chemotherapy treatment, the ESR1 mutations remain an important driver of tumor growth and metastases and therefore drugs targeting the ESR1 mutation could enhance the efficacy of chemotherapy. In this study we investigated the combination of chemotherapy with the selective estrogen receptor degrader in the presence of WT and mutant ER. Methods: We performed synergy studies testing the combination of fulvestrant with chemotherapy treatments commonly used in ER+ metastatic breast cancer including 5FU (representing capecitabine), adriamycin and paclitaxel using MCF7 and T47D breast cancer cell lines engineered to express doxycycline inducible Y537S-ESR1 mutation. Results: We found that in MCF7 cells the combination of chemotherapy and fulvestrant was synergistic and the synergy was augmented with the induction of the Y537S mutation. In contrast, there was no synergy in T47D cells that harbor a P53 mutation. We confirmed that the synergistic activity of fulvestrant with chemotherapy is dependent on P53 by generating P53 knock-out MCF7 cells using CRISPR-cas9. Additionally, cell cycle and apoptosis analyses showed that the synergistic activity was mainly due to increased effects on G1 arrest rather than apoptosis. Conclusions: Our study indicates that chemotherapy and fulvestrant are synergistic in ER+ breast cancer and the synergy is increased in the presence of the Y537S ESR1 mutation and is dependent on P53 activity. These results support a clinical trial testing the addition of fulvestrant or other novel selective estrogen receptor degraders in patients with metastatic ER+ breast cancer who are starting chemotherapy treatment.
PIK3CA mutation status and progression-free survival in advanced hormone receptor positive (HR+)/ human endocrine receptor negative (HER2–) metastatic breast cancer (mBC): A meta-analysis of published clinical trials.
Authors: Signorovitch James , Andre Fabrice , Wang Ruchuan , Lorenzo Ines , Ridolfi Antonia , Park Jinhee , Fillbrunn Mirko , Dua Akanksha , Rugo Hope S.
Published: May 2020

1069

Background: Approximately 40% of HR+/HER2- mBC patients harbor PIK3CA mutation. Associations between PIK3CA mutation status and clinical outcomes among patients with HR+/HER2- mBC have been heterogeneous across clinical trials. We synthesized available evidence from clinical trials to estimate the association between PIK3CA status and progression-free survival (PFS) using a meta-analysis adjusting for study design differences. Methods: Randomized clinical trials reporting PFS stratified by PIK3CA status in HR+/HER2- mBC were identified via a systematic literature review. Trial arms receiving PIK3CA targeted therapies were excluded. Median PFS, 6-, 12- and 18-month PFS rates, and data on trial design features were extracted. Associations between PIK3CA status and PFS were estimated adjusting for study follow-up duration, PIK3CA testing method (ctDNA vs tissue ) and study treatment using multi-level random effects meta-regression. Results: The analyzed data included 3,238 patients from 33 study arms across 11 trials ( PIK3CA mutated (MT): 1,386, wild type (WT): 1,852). PIK3CA mutation was overall associated with shorter median PFS (difference [95% CI] (months): -2.15 [-4.14, -0.15]) with substantial heterogeneity across studies ( I2 = 98.34%). The direction of this association was robust to adjustment for study treatment (-1.27 [-2.22, -0.32]). The association was stronger for ctDNA testing (-2.16 [-3.65, -0.66]; N (total patients): 1,876) than for tissue testing (-0.65 [-2.2, 0.91]; N: 998). Findings were similar for 6-month PFS rates (absolute rate difference -9.17% [-14.22, -4.12], N: 3,179; MT: 1,366, WT: 1,813). Associations were directionally consistent but not statistically significant at 12 months (N = 2,487; MT: 1,056, WT: 1,431) and 18 months (N = 1,745; MT: 811, WT: 934), potentially due to the decreasing precision towards the tails of the PFS curves and significant heterogeneity across studies. Conclusions: Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS, especially when ctDNA testing was used. These findings suggest a negative prognostic value of PIK3CA mutation in patients with HR+/HER2- mBC.
RNA sequencing analysis and T-cell receptor repertoire in triple-negative breast cancer (TNBC).
Authors: Kim Ju Won , Yu Yun Suk , Choi Jung Yoon , Lee Soohyeon , Chang Won Jin , Choi Yoon Ji , Jung Seung Pil , Kong Sun-Young , Sim Sung Hoon , Lee Keun Seok , Park Jin Young , Seo Yong Bae , Kim Yeul Hong , Lee Eun Sook , Park Kyong Hwa
Published: May 2020

1075

Background: Triple negative breast cancer (TNBC) is defined by the lack of two hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2), and well known to have poor prognosis. In this study, we conducted a RNA sequencing including T-cell receptor (TCR) repertoire analysis to develop prognostic biomarker in patients with TNBC. In addition, genes and signaling pathways that correlated with selected biomarker were also investigated. Methods: Total of 78 tumor tissues from TNBC patients were participated for RNA-seq (Illumina Hiseq) analysis. Groups of significant genes were selected by differentially expressed genes (DEGs) analysis, whose expression levels differed more than 1.5 times between patients and normal, or early stage and advanced stage TNBC. Transcript expression levels for prognostic biomarker were analyzed based on R v3.4.3. Using CBS ProbePINGS, a genomic big data analytics platform, we evaluated druggable pathways and protein-protein interaction (PPI). The Interaction Frequency Ratio Score (IFRS) was calculated by investigating highly interactive pathways, and the drugs were matched to patients. TCR repertoire analysis was performed by MiXCR. Results: Ten candidate gene signatures were selected based on RNA sequencing data of each sample. Cross-validation through machine learning showed that the accuracy of the first-ranked signature was 92.3%, the second was 92.0%, and the third was 90.3%. The accuracy of 4th to 6th was 88.7%, and the accuracy of 7th to 10th was over 88.0%. Cross-validated gene signature, age, and TNM staging showed significant discriminant power under univariate Cox regression analysis (p < 0.05). In the CBS ProbePINGS, human papillomavirus infection, MAPK pathway, and tumorigenesis pathway were correlated with cell signaling. CDK2, FN1, and JUN genes were highly interactive each other. In addition, the drug matching result according to IFRS value suggested imatinib and regorafenib could be possible candidates. TCR repertoire analysis presented that number of clonecount was lower in recurrent or metastatic TNBC than early stage cancer. Conclusions: This study revealed a specific gene signatures that can accurately determine recurrence and metastasis in patients with TNBC based on RNA sequencing analysis. TCR repertoire analysis and CBS ProbePINGS could be valuable method in treatment selection
Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors.
Authors: Hafez Navid , Soliman Hatem Hussein , Fu Siqing , Gelmon Karen A. , Abdul Razak Albiruni Ryan , Munster Pamela N. , Vaishampayan Ulka N. , Kato Shumei , Lara Primo , Swisher Elizabeth M. , Nixon Andrew B. , Patel Abhijit , Shyr Yu , Ivy S. Percy , LoRusso Patricia , Kim Joseph W.
Published: May 2020

1077

Background: Cediranib, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in patients with germline BRCA1/2 mutations and HER2-negative metastatic breast cancer. We therefore tested the anti-tumor activity of the combination of cediranib and olaparib in patients (pts) with metastatic triple-negative breast cancer (TNBC). Methods: This multi-institutional, two-stage, phase II study enrolled patients with metastatic TNBC previously treated with a minimum of one prior line of systemic therapy in the advanced setting. Patients were treated with cediranib 30mg po daily plus olaparib 200mg po BID until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by RECIST v1.1. Baseline tumor biopsies were obtained for biomarker analyses. Results: Baseline characteristics of the 37pts enrolled are summarized below. The overall objective response rate was 14% (95% CI: 0.025, 0.2453). Median duration of response was 2.0 months (mos) with a range of 1.8 to 6.3 mos. Disease control rate ((# of pts with CR, PR or SD)/(# of evaluable pts)) was 81% (95% CI: 0.6846, 0.937). Median PFS was 3.7 mos (95% CI: 2.1, 4.3). Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 25 of 38 (66%).G3/4 AEs occurring in > 5% of pts were hypertension (24%) and dyspnea (11%), diarrhea (8%) vomiting (8%). Conclusions: The cediranib/olaparib combination resulted in promising objective responses in 14% of biomarker-unselected patients with heavily pre-treated, metastatic TNBC. The regimen required prompt initiation of antihypertensives, but AEs were overall manageable. Analyses of mutation status in homologous recombination DNA repair genes are ongoing and will be correlated with clinical outcome. Clinical trial information: NCT02498613 . [Table: see text]
Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).
Authors: Nasrazadani Azadeh , Li Yujia , Tseng George , Xavier Jennifer , Lee Adrian V. , Lucas Peter C. , Oesterreich Steffi , Wolmark Norman
Published: May 2020

1085

Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p < 0.001), and less likely to have metastasis to the peritoneum (p < 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.
Innovation in resident oncology education: Switching from an inpatient ward rotation to a hybrid model of inpatient consultations and outpatient clinics.
Authors: King Jennifer , Saliba Antoine , Akel Reem , Wei Cynthia , Manchanda Naveen , Sinex Noelle , Grethlein Sara Jo , Goldman Mitchell
Published: May 2020

11006

Background: Interest in pursuing a career in oncology has decreased among internal medicine residents completing an inpatient oncology rotation. Over several years, our institutional data at Indiana University School of Medicine reflected lower resident satisfaction with the oncology inpatient ward rotation compared to other rotations. Methods: A hybrid model of inpatient consultations and outpatient clinics replaced the traditional inpatient oncology rotation at our institution. Over a six-month period preceding and following the change in format, residents completed anonymous rotation assessments and rated their experiences on a 5-point Likert scale (low 1 to high 5). Areas assessed included: patient load, educational value of patient mix, quality of didactics and teaching, quality of patient care delivery, adequacy of time for reading, and overall educational quality of the rotation. Results: The hybrid oncology rotation (8 respondents out of 10 residents approached) was rated as significantly superior to the traditional ward format (15 respondents out of 16 residents approached) in six out of eight areas. Improvements in the perceived quality of patient care delivery (p=0.139) and quality of didactics (p=0.058) were also observed without reaching statistical significance. The balance of inpatient and outpatient experiences with the hybrid rotation was highly rated (4.5 ± 0.5). Conclusions: The implementation of a hybrid oncology rotation was associated with perceived improvement in educational value, patient mix, and time for reflection and study without apparent compromise in the quality of patient care delivery. [Table: see text]
Storytelling as a means of improving community and decreasing burnout in a large academic cancer center.
Authors: Rogers Sherise C. , Benson Don M. , Kraut Eric H. , Haque Tamanna Zohra , Mousa Luay , Fowler Jeffery , Dettorre Janet
Published: May 2020

11018

Background: Burnout is highly experienced amongst physicians who care for patients with cancer. Workplace isolation is a risk factor for burnout. The field of oncology is growing at a rapid pace and many cancer centers are expanding to meet the demands of patient care and research. Prior assessments revealed that our hematology and oncology fellows were experiencing feelings of isolation and disconnection, which was likely reflected from our greater academic community. Methods: The traditional art of storytelling has been used to offer guidance, teaching, new perspective taking and understanding of self. The concept of “My Story”, an interactive storytelling lecture series was developed to address the following objectives at a large academic cancer center: 1) Promote connection and decrease isolation amongst the cancer sub-specialties 2) Increase fellow-faculty interaction for mentorship, 3) provide an outlet to discuss sensitive topics such as burnout, grief, unexpected patient outcomes, medical errors, work- life balance, career transitions, personal struggles, and bias. A faculty member was identified to tell their unique story for a special lecture. Fellows and faculty members from hematology, oncology, radiation-oncology, neuro-oncology, gynecology-oncology, and surgical oncology were invited. All audience members were encouraged to ask questions and engage in discussion. A survey was distributed after the inaugural event for evaluation. Results: A total of 56 people attended the inaugural event. There were 14 fellows, 9 faculty members and 33 others, which included basic scientists and advance practice providers. 17 individuals completed our post survey, which included 6 faculty members, 4 fellows, 1 nurse practitioner, 1 student and 5 others. On a scale from 1-10 (mean scores reported), participants rated the experience 7.5 for enjoyment, 6.6 for sense of connection with the group, 6.0 for inspiring them to make new connections with others and 6.8 when asked if they left with new tools to assist with personal challenge. Conclusions: A lecture series that invites multidisciplinary cancer physicians and surgeons to discuss personal career and life challenges can be beneficial to addressing burnout, decreasing isolation and improving connection and community at a large academic cancer center.
Reflection rounds to facilitate resilience in hematology/medical oncology fellows.
Authors: Nakajima Erica C. , Murray Joseph Christopher , Zimmerman Jacquelyn W. , Messmer Marcus , Waseem Najeff , Nizialek Emily , Sedhom Ramy , Gupta Arjun , Donehower Ross C. , Marrone Kristen
Published: May 2020

11019

Background: Given the prevalence of burnout among medical oncologists (40-60% in the literature), education on burnout risk factors, recovery, and prevention are needed urgently in training curricula for medical oncology fellows. Care of patients with cancer is increasingly complex, and often can seem overwhelming to new trainees. Debriefing as a resiliency skill to develop self-reflection and identify coping strategies may provide a durable way to navigate these complexities. Optimization of fellowship Reflection Rounds (RR) was selected as a fellow-led quality improvement (QI) project for the current academic year. Methods: A QI team including the APD and representatives from all levels of fellowship training was assembled. Feedback regarding previously unstructured, monthly, hour long faculty-facilitated RR for first year fellows was reviewed. Topics with associated readings were selected and paired with fellow-nominated faculty based on the most common recurring themes. The QI team administered the Stanford Professional Fulfillment Index (PFI) to all fellows at the midway point of the academic year. RR were re-structured to include a chaplain with trainee communication expertise and a chief fellow to participate the sessions to assess changes in trainee engagement. Repeat assessment of the Stanford PFI is planned for the end of the academic year. Results: Topics identified for discussion included handling bias, futile care, patient communication, end of life care, and work-life balance. 26 fellows completed the Stanford PFI including nine 1st year fellows, 13 2nd year fellows, and 6 3rd year fellows. Survey results revealed emotional and/or physical fatigue as areas of greatest need for improvement in fellow well-being with 27% of fellows reporting “moderate” emotional or physical exhaustion. Conclusions: RR provides a safe and effective forum to develop peer debriefing and self-refection as resiliency skills within hematology/medical oncology fellowship training. Optimization of RR will continue as fellows become more involved in planning and implementation of curricular improvements to promote resiliency and enhance wellness.
Practice gaps and challenges integrating new immuno-oncology agents in the treatment of cancer patients in the United States: A mixed-method study.
Authors: Ready Neal E. , Parikh Aparna Raj , Lazure Patrice , Peniuta Morgan , Davies Marianne , Augustyniak Monica , Caterino Jeffrey , Lewandowski Robert , Lazar Alexander J. , Murray Suzanne
Published: May 2020

11028

Background: Previous research has indicated challenges integrating new immuno-oncology agents (IOAs) and predictive immune biomarkers into practice. Barriers, clinical gaps and underlying causalities explaining these challenges, however, are poorly understood. Methods: A mixed-methods educational needs assessment was conducted with physicians from 6 specialties (oncology, interventional radiology, pathology, pulmonology, emergency medicine and rheumatology), clinical pharmacists, physician assistants and advanced nurse practitioners involved in the care of cancer patients in the United States. Semi-structured interviews and discussion groups were thematically analyzed to identify challenges, barriers and underlying causalities. Qualitative findings subsequently informed the development of online surveys, which served to quantify findings. The following findings pertain to oncologists. Results: A total of 660 health care providers participated in the study, in which 17 interviews and 88 surveys were completed with oncologists. Seventy-two percent reported sub-optimal knowledge of the interactions between IOAs and the tumor’s micro-environment, while 62% reported sub-optimal skills determining which IOA to select based on this information. Oncologists reported sub-optimal knowledge of best practices for using IOAs to treat cancer in presence of an autoimmune disease (74%-80% depending on condition), and sub-optimal skills weighing the risks and benefits of prescribing IOAs for these profiles (66%-77%). In addition, 50% of oncologists reported feeling overwhelmed by the volume of new IOAs being made available. Many oncologists expressed doubts regarding the clinical benefit (59%) and innovative nature (43%) of emerging IOAs. Finally, 46% reported limited skills identifying viable treatment options based on pharmacodiagnostic test reports. Barriers to having predictive biomarkers inform treatment decisions included sub-optimal communication between specialists regarding specimen requirements and desired biomarker information. Conclusions: This study demonstrates the need to further support healthcare professionals as they face challenges integrating new IOAs and predictive immune biomarkers into practice. Given the wide array of IOAs becoming available each year, addressing the knowledge, skills, confidence and attitude gaps identified in this study could help improve health care delivery and potentially optimize outcomes for cancer patients.
Content analysis of pancreatic cancer conversations on Twitter: What matters most to users?
Authors: Grewal Udhayvir Singh , Doggett Jamie , Lou Emil , Ocean Allyson J. , Gusani Niraj Jaysukh , Gupta Arjun , Maitra Anirban , Beg Muhammad Shaalan
Published: May 2020

11040

Background: Social media has an important role in addressing medical misinformation by connecting the global community of health care professional (HCP), cancer patients and advocates. We evaluated the content and dynamics of discussions around pancreatic cancer (PC) on Twitter to identify subtopics of greatest interest to these users. Methods: We used online analytical tool (CREATION Pinpoint) to quantify Twitter mentions (tweets and re-tweets) related to PC between 1/2018 to 12/2019. Keywords, hashtags, word combinations and phrases were used to query for PC mentions. HCP profiles were identified using machine learning and then human verified and remaining user profiles were classified as general public (GP). Data from conversations were analysed and stratified qualitatively (using e.g keywords/combinations/phrases) into 5 categories; 1) prevention (P), 2) survivorship (S), 3) treatment (T), 4) research (R), and 5) policy (Po). We analysed the impact of PC awareness month (PCAM) and celebrity PC diagnosis on the overall level of conversations. Results: Out of 1,258,028 mentions on PC, 313,668 unique mentions were classified into the 5 categories. We found that HCP discuss PC research more than the GP, while GP are more interested in treatment. PCAM did not increase mentions by HCP in any of 5 categories while GP mentions over 2 years, increased temporarily in all categories except prevention. HCP mentions did not increase with celebrity PC diagnosis. Alex Trebek’s diagnosis increased GP mentions on survivorship, while Ruth Ginsburg’s diagnosis increased conversations on treatment (Table). Conclusions: Twitter mentions between HCP and GP around PC are not aligned. The HCP conversation was mainly limited to research while GP were more interested in treatment. PCAM temporarily increased GP conversations around treatment, research, survivorship and policy but not prevention. Future studies should address which factors determine how celebrity diagnoses drive conversations. [Table: see text]
Patterns of Twitter use among trainees in hematology-oncology related areas.
Authors: Gonzalez Velez Miguel , Duma Narjust , Cabrera Daniel , Marshall Ariela L. , Attai Deanna J. , Markham Merry Jennifer , Fonseca Rafael
Published: May 2020

11041

Background: Twitter (TW) is an essential tool in the medical community. Few studies have examined the use of TW by medical trainees. We aimed to assess its utilization among trainees in hematology-oncology related areas (HORAs). Methods: 576 training programs in HORAs were obtained. We contacted a potential pool of 3,142 trainees. A 50 item survey was distributed between 2/2019-5/2019, focusing on: demographics, professional use, attitudes toward TW, and patient interactions. Responses were analyzed using parametric descriptive statistics. Results: 442 responses (14% response rate) were received; 203 (46%) used a TW account for professional activities. See table for demographics. The most common reasons for using TW were: continuous education (73%), dissemination of information (62%), and networking (62%). > 80% of users have positive views on using TW for: promoting academic discussions (92%), trainees education (89%), and conference networking (83%). 50 (25%) have used TW for collaborations, with abstracts and papers being the most common (20%). Most agreed or strongly agreed that TW: is a useful education tool (89%), and might be useful for career advancement (85%). The most common challenges were: the value of TW content can be decreased by irrelevant content and biased sources (64%), not peer-reviewed (51%), and difficulty searching information (50%). 68% considered that programs should promote the engagement of trainees, but only 21% reported instruction in the use of TW. 83% agree or strongly agree that TW is useful for physicians and patient interactions, but 82% have concerns about legal repercussions. Conclusions: Almost half of trainees in HORAs use TW for professional activities. The most common uses are for education, dissemination of information and networking. Most trainees that use TW have positive views regarding education and academic collaborations. Use of Twitter may strengthen trainees’ education, provide mentorship opportunities, and promote career advancement. Challenges on TW use should continue to be addressed. [Table: see text]
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 .