tbuckley/cabot-search huggingface dataset:
Survival outcomes of breast cancer patients with brain metastases: Single center experience from Northern India.
Authors: Hari Krishna Raju Sagiraju, Ajay Gogia, Dayanand Sharma, S. V. S. Deo, Sandeep Mathur
Journal: Journal of Clinical Oncology (2021)

e13003 Background: Brain metastasis (BM) is a poor prognostic factor for survival among breast cancer (BC) patients. Very few studies reported in the literature have challenged this premise, suggesting that time to the occurrence of brain metastasis and the survival times following brain metastasis differ significantly between BC subtypes. The purpose of this study was to evaluate the clinico-pathological characteristics associated with brain metastasis free survival (BMFS), survival after brain metastases (SABM) and overall survival among Indian women with BC and BM. Methods: Among 621 patients treated for metastatic BC from 2015 to 2018 at All India Institute of Medical Sciences-New Delhi, 79 (12.7%) patients were identified to have BM. Of these ten individuals have presented with BM at the time of presentation. Survival analysis and Cox proportional hazards models were fitted to explore clinco-pathological factors that are associated with survival outcomes in these individuals. Results: Median age of the sample is 42 years (range:22-64). Triple negative breast cancers (TNBC) accounted for 25.3% and HER2 positive were 49.4% in our sample. Median time for the occurrence of BM from cancer diagnosis was 20.5 months (95% CI:14.7-26.2) in the overall sample, while among TNBC and HER2 positive tumors was 14.1 and 20.6 months respectively. In Cox multivariable model, T4stage [Hazard Ratio (HR) (95%CI): 2.4(1.1-5.3)], having a metastatic disease other than to brain at the time of presentation [HR(95%CI): 2.8(1.5-5.4)] and TNBC [HR(95%CI): 2.7(1.1-6.7)], was observed to be significantly associated with BMFS. Median SABM was 7.9 months (95% CI 5.2–16.2) and the median overall survival from the cancer diagnosis was 32.4 months (95% CI 23.4–40.8). Adjusted for age, only the presence of multiple brain lesions (&gt;2) was significantly associated with SABM [HR (95%CI): 2.4(1.1-5.2)]. However, TNBC [HR (95%CI): 2.9(1.2-7.4)]and baseline metastatic disease [HR (95%CI): 2.2(1.2-4.2)] were significantly associated with overall survival following cancer diagnosis in these individuals. HER2 positivity was not associated with BMFS or SABM in this cohort. Conclusions: In this single-institutional study, clinical T4 stage, TNBC subtype and baseline metastatic disease have shown to be significantly associated with BMFS and overall survival. These results suggest that women in Indian population with these baseline clinico-pathological characteristics at the diagnosis of breast of cancer should be frequently monitored for BM.
<sup>125</sup>I seed combined with DCS loaded with tumor antigen to convert irradiated liver cancer into effective in situ vaccine.
Authors: Peng Zeng
Journal: Journal of Clinical Oncology (2021)

e14573 Background: With unique feature of self-immune tolerance and high radio-sensitivity, hepatocellular carcinoma (HCC) can gradually develop undesired effects. Iodine-125 ( 125 I) seed, as a source of internal radiation therapy, may have a favorable adaptability and immunostimulation. In this study, we investigated whether 125 I seeds can stimulate local tumor infiltrating lymphocytes (TILs) and whether a combination of 125 I seeds and dendritic cells (DCs) loaded with tumor antigen (Ag + DCs) can enhance both local tumor control and abscopal effect in murine subcutaneous tumor models. The related mechanism of anti-tumor immune response was also explored. Methods: H22/Hepa1-6 HCC cells were examined for radiosensitivity and immunosensitivity. Cell apoptosis and expression of MHC-I (major histocompatibility complex class I) and PD-L1 (programmed death-ligand 1) were detected before and after irradiation. The tumor cells were injected subcutaneously as primary and abscopal tumor. Bone marrow-derived dendritic cells (BM-DCs) were induced from mouse bone marrow cells and incubated with tumor cell lysate. 125 I seeds were implanted into the primary tumors, followed by intratumoral injection of Ag + DCs and intraperitoneal injection of αPD1 antibody (αPD1-ab). DC migration was detected by transwell chambers in vitro and CFSE (carboxyfluorescein succinimidyl ester)-labeled DCs in vivo. DC maturation was tested by flow cytometry. Analyses of tumor growth and survival rates were performed in vitro, and that of, TILs, T-cell proliferation, cytotoxicity test, immunostimulatory cytokines release, and immunological memory were performed in vivo. In situ vaccine and abscopal effect were verified in orthotopic mouse models of liver cancer and lung metastatic tumor. Results: 125 I seeds alone could induce TILs and activate cytotoxic T cells (CTLs), but these effects were limited. The combination treatment of 125 I seeds with Ag + DC administration inhibited primary tumor growth and significantly prolonged survival time in association with a significant increase in T-cell proliferation and interferon-γ release. In addition, triple-combination treatment with αPD1-ab amplified these responses, leading to significant regression of primary and metastatic tumors and successful stimulation of immunological memory. Conclusions: 125 I seeds can safely activate anti-tumor immune response. 125 I seeds combined with Ag + DC administration is able to convert irradiated liver cancer into effective in situ vaccine. Furthermore, triple-combination therapy of 125 I seeds, Ag + DC, and αPD1-ab can be a promising approach to activate systemic anti-tumor immunity, which is a potential novel individualized therapy for patients with solid cancers.
FOENIX-CCA2 quality of life data for futibatinib-treated intrahepatic cholangiocarcinoma (iCCA) patients with <i>FGFR2</i> fusions/rearrangements.
Authors: Juan W. Valle, Antoine Hollebecque, Junji Furuse, Lipika Goyal, Funda Meric-Bernstam, Robert S. Epstein, Tehseen Salimi, Volker Wacheck, Mei Liu, Karim A. Benhadji, John A. Bridgewater
Journal: Journal of Clinical Oncology (2021)

4097 Background: In FOENIX-CCA2 (NCT02052778), a pivotal phase 2 study among iCCA patients (pts) with FGFR2 fusions/rearrangements, the highly selective, irreversible FGFR1–4 inhibitor futibatinib demonstrated a confirmed objective response rate of 41.7%, with a 9.7-month median duration of response. Adverse events were manageable with dosing modifications that did not adversely impact on response. We report outcomes for the preplanned analysis of Patient-Reported Outcomes (PROs) during futibatinib treatment as a secondary objective of FOENIX-CCA2. Methods: Pts enrolled in FOENIX-CCA2 had locally advanced/metastatic unresectable iCCA with FGFR2 fusions/rearrangements, ≥1 prior line of therapy (including gemcitabine/cisplatin) and ECOG PS 0-1. Pts received oral futibatinib 20 mg continuous QD dosing per 21-day cycle. PRO measures included EORTC-QLQ-C30 (1 global health, 5 functional, 9 symptom scales), EQ-5D-3L, and EQ visual analogue scale (VAS). PROs were collected at screening, cycles 2 and 4, every 3 cycles thereafter, and end of treatment. PRO data were evaluated up to cycle 13, the last visit before data were missing for &gt;50% of the PRO population (PRO primary assessment time point). Results: 92/103 (89.3%) pts enrolled had PRO completion data at baseline and a minimum of 1 follow-up assessment (median age 58 y, 56.5% female), with 48 pts having PRO data at cycle 13. At baseline, mean (SD) EORTC QLQ-C30 global health status score was 70.1 (19.4) and EQ VAS score 71.7 (20.3). Mean EORTC QLQ-C30 global health status scores were maintained from baseline to cycle 13, corresponding to 9.0 months on treatment, with no clinically meaningful (≥10-point) changes in individual functional measures (Table). EORTC QLQ-C30 scores across individual symptom measures were also stable from baseline through cycle 13; only constipation showed an average of 10.0-point worsening at only cycle 4. Mean EQ VAS scores were sustained from baseline to cycle 13 (mean change ranging -1.8 to +4.8 across cycles), with values maintained within the population norm range from across 20 countries. Conclusions: Quality of life data from the phase 2 FOENIX-CCA2 trial show that physical, cognitive and emotional functioning, and overall health status were maintained among pts with advanced iCCA receiving futibatinib. Clinical trial information: NCT02052778. [Table: see text]
Baseline level and early on-treatment clearance of circulating mutant <i>KRAS</i> in metastatic pancreatic ductal adenocarcinoma treated with chemotherapy with or without immunotherapy.
Authors: Jacob E. Till, Aseel Abdalla, Neha Bhagwat, Taylor A. Black, Zhuoyang Wang, Stephanie S. Yee, Pier Federico Gherardini, Lacey J. Kitch, Cheryl Selinsky, Jaclyn Paige Lyman, Theresa LaVallee, George A. Fisher, Osama E. Rahma, Andrew H. Ko, Zev A. Wainberg, Robert A. Wolff, Eileen Mary O'Reilly, Robert H. Vonderheide, Mark H. O'Hara, Erica L. Carpenter
Journal: Journal of Clinical Oncology (2021)

4122 Background: Traditional imaging-guided therapeutic decision-making for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) may lag and, on occasion, be misleading. The concept of liquid biopsy-based molecular response holds promise for proximate and accurate therapy monitoring and assessment of emerging resistance to therapy. Here we investigate the association between baseline (pre-treatment) level and early, on-treatment changes in plasma circulating cell-free DNA (ccfDNA) mutant KRAS (ctKRAS) with progression-free survival (PFS) and overall survival (OS) in mPDAC. Methods: 189 plasma samples were analyzed from 123 total patients with mPDAC. An initial cohort included 54 patients treated at the University of Pennsylvania who received first-line standard of care (SOC) regimens and had a baseline plasma sample. Of these, 21 also had an on-therapy sample collected at ̃8 weeks. We also analyzed an independent cohort of 69 patients enrolled in the PRINCE trial (NCT03214250) who had a baseline sample, of which 45 also had an on-treatment sample at ̃8 weeks. PRINCE trial patients received gemcitabine/nab-paclitaxel with immunotherapy (I/O) agents (APX005M and/or nivolumab). ctKRAS variant allele fraction (VAF) was quantified by droplet digital PCR on pre-amplified ccfDNA. Baseline ctKRAS was dichotomized at 5% VAF. ctKRAS clearance was defined as detectable ctKRAS at baseline followed by ctKRAS becoming undetectable in the on-treatment sample. Results: Baseline ctKRAS (above/below 5% VAF) and ctKRAS clearance were associated with PFS and OS in both cohorts (Table). Further, in a multivariate cox regression model, ctKRAS clearance associated with improved PFS (HR 3.8, 1.4-10.9 or 3.6, 1.8-7.2) in both the SOC and I/O cohorts, respectively, and OS in the SOC cohort (HR 5.5, 1.5-20.8) after adjusting for baseline VAF. Conclusions: Baseline ctKRAS is significantly associated with OS and PFS in mPDAC in both independent cohorts. Further, early on-treatment ctKRAS clearance is strongly associated with improved PFS and OS, independent of baseline ctKRAS VAF. These data strongly support further investigation of ccfDNA as a biomarker of response and resistance to therapy.[Table: see text]
Abstract 15904: Effect of Menopausal Hormonal Therapy and Coronary Artery Calcium on Volumetric Bone Mineral Density by Serial Computed Tomography Angiography
Authors: Chandana Shekar, April Kinninger, Lucas Cespedes, Eranthi Jayawardena, Lavanya Cherukuri, Divya Birudaraju, Matthew J Budoff, Sion K Roy
Journal: Circulation (2019)

Introduction: Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions. Hypothesi...
Survival impact among occidental patients with metastatic gastric cancer (mGC) treated with ramucirumab as second line treatment (2L): Local experience of a teaching hospital in Chile.
Authors: Carlos Salinas, Olga Barajas, Luis Villanueva, Rodrigo Vasquez, Monica Ahumada
Journal: Journal of Clinical Oncology (2021)

e16007 Background: GC is frequent in Chile, with an incidence of 7.8% and a mortality rate of 11.6% in 2020. Late diagnosis continues to be one of the most important problems, although treatments in advanced stages have experienced important advances in the last 6 years. REGARD and RAINBOW trials showed an increase in median OS when using Ramucirumab alone or in combination with Paclitaxel of 5,2 and 9,4 mths respectively. Although this therapy is not covered by our Public Health Insurance, there are some patients that they can access. Also, there are not too many reports in LATAM pts so we present our local real world data. Methods: We conducted a retrospective study of local data from patients diagnosed with mGC who progressed with standard first-line treatment and were treated with ramucirumab-based regimens from January 2015 to January 2021. Clinical factors were recorded baseline, characteristics of therapy and AE related to toxicity. Toxicity was assessed by CTCAE v5.0 and response to treatment by RECIST 1.1. Results were analyzed by measuring time to progression and survival. Results: The search resulted in 9 pts, 6 men and 3 women between 38 and 72 years (median 59 years). 66% were in ECOG 1 performance status and 33% in ECOG 2, with a median BMI of 23 kg / m2. 33% were smokers and all had some other comorbidity as a medical history. All tumors were adenocarcinomas and 33% had a signet ring cell component on histology. Only one tumor was HER2 +++ and all were MSS (by IHC). The most common first-line treatment received before progression was FOLFOX; 4 to 12 cycles; 8 cycle average. All patients were treated with paclitaxel-ramucirumab as 2L (4 to 19 cycles, mean of 5 cycles). 67% of patients achieved stable disease with the best response. During the follow-up period, 8 patients experienced disease progression in an average of 6.7 months, who switched to 3L with Nivolumab. Relapses during 2L were in the peritoneum and 55% in other sites as well. Only two patients discontinued paclitaxel treatment after 4 cycles due to intolerance and continued to receive Ramucirumab. 44% developed grade 3 toxicities: 50% of them due to taxane-related peripheral neuropathy. Grade 4 or 5 toxicity was not reported. 50% of patients were alive at 6 months of treatment. Conclusions: In our country and LATAM, GC still has a significant medical and socioeconomic burden. Its incidence is still one of the highest in the world, most patients are diagnosed in the metastatic stage and face treatment in deficient PS. In this context, our local real-world data showed consistency with what the literature says, although more data remains to accumulate and describe.
Early results of phase 1 study of JSP191, an anti-CD117 monoclonal antibody, with non-myeloablative conditioning in older adults with MRD-positive MDS/AML undergoing allogeneic hematopoietic cell transplantation.
Authors: Lori S. Muffly, Michelle Chin, Hye-Sook Kwon, Cara Lieber, Steven Smith, Robert Sikorski, Judith Shizuru, Wendy Pang, Andrew S. Artz
Journal: Journal of Clinical Oncology (2021)

7035 Background: Myeloablative allogeneic hematopoietic cell transplantation (AHCT) is potentially curative for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but toxicities of conditioning limit its use in older or frail patients. Non-myeloablative (NMA) conditioning achieves better tolerability, at the expense of higher rates of relapse. We have developed a first-in-class monoclonal antibody (mAb), JSP191, which inhibits stem cell factor binding to CD117 (c-Kit), thereby depleting normal and MDS/AML disease-initiating hematopoietic stem cells (HSC). In pre-clinical models, anti-CD117 mAbs potently synergize with low dose total body radiation (TBI) to deplete HSC and facilitate donor cell engraftment. We reasoned that adding JSP191 to a standard NMA conditioning of 2 Gy TBI and fludarabine (Flu) would be safe and result in depletion of measurable residual disease (MRD) in older adults with high-risk MDS/AML entering AHCT. Methods: We report on the first 6 enrolled subjects in our Phase 1 trial (NCT#04429191) of JSP191/TBI/Flu as AHCT conditioning in MDS/AML patients, ≥ 60 years, with MRD detected by cytogenetics (cyto), difference from normal flow cytometry (flow), and/or next-generation sequencing (NGS). Primary endpoints are safety and tolerability of JSP191/TBI/Flu and JSP191 pharmacokinetics. Secondary endpoints include engraftment, donor chimerism, MRD clearance, GVHD, NRM, EFS, and OS at 1 year. JSP191 at 0.6 mg/kg was administered intravenously; serum concentration of JSP191 was used to confirm timing to begin Flu at 30 mg/m 2 /day x 3 days [Transplant Day (TD)-4, -3, -2] and TBI 2 Gy on TD0. Peripheral blood grafts from HLA-matched related or unrelated donors were administered on TD0 (10-13 days after JSP191). GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. Results: All subjects are still on trial, and there have been no infusion toxicities and no JSP191-related serious adverse events. All subjects engrafted with neutrophil recovery TD+19 to TD+26, and showed ≥94% donor myeloid chimerism in the blood at TD+28. All 3 evaluable subjects with TD+90 follow up showed complete donor (≥95%) total and myeloid chimerism and MRD elimination (Table). Conclusions: These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Clinical trial information: NCT04429191. [Table: see text]
Infographic. A guide to understanding athlete abuse
Authors: Yetsa A Tuakli-Wosornu
Journal: British Journal of Sports Medicine (2021)

With increasing frequency, reports of interpersonal violence (eg, abuse) are emerging from sport settings, across a range of sports.1–3 Individual sports with female-dominated membership statistics, feminine gender culture and low clothing levels (gymnastics, swimming) seem especially vulnerable to systemic abuse, and team sports with male-dominated gender structure, masculine gender culture and high clothing levels (ice hockey, American football) are also affected. Thus, it is clear that interpersonal violence is prevalent across a range of sport settings. But it can be difficult to understand.



This is because there are a range of athlete harms, various antecedent risk factors (structural, cultural, interpersonal), and a host …
Patient care and clinical trials in gynecological oncology: Implications of the COVID-19 pandemic.
Authors: Sara Nasser, Christina Fotopoulou, Murat Guktekin, Desislava Dimitrova, Philippe Morice, Jalid Sehouli
Journal: Journal of Clinical Oncology (2021)

5564 Background: This is a prospective international Survey to evaluate the impact of the COVID-19 Pandemic on the management of patients with gynecological malignancies from the multidisciplinary physicians' perspective, with particular focus on clincial infrastructures, and trial participation. Methods: The anonymous online survey consisted of 53 COVID-related questions. It was sent to all healthcare professionals in gynaecological oncology centres across Europe and the Pan-Arabian region from April 2020 to October 2020. All healthcare professionals treating women with gynecological cancers were able to participate in the survey. Results: A total of 243 answers were collected from 30 different countries. The majority (73%) of participants were gynecological oncologists from university hospitals(71%) with at least an Intensive care unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years(range 0-12 weeks). Cases that were prioritised for surgical intervention across all tumors (Ovarian, Endometrium, Cervical) were early stage disease (74%), primary situation (61%), and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumor types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. 45% stated the pandemic has negatively impacted the financial structure and support for clinical trials. 79% do not routinely screen patients included in trials for SARS CoV2. Overall, approx. 20% of clinicians did not feel well informed regarding clinical pathways for COVID-19 patients throughout the pandemic. The majority preferred regular updates and training via Webinars (75%), followed by tumorboards and interdisciplinary conferences (45%). 30% of clinicians stated that they are currently experiencing difficulties in providing adequate medical care due to staff shortage. Conclusions: Despite well-established guidelines for patient care and performing clinical trials in gynecological oncology, the COVID-19 pandemic has impacted clinical research, and financial structures. Longer waiting times for operative interventions, less support for clinical trials and concerns regarding provision of adequate medical care and triaging patients are very real. This survey underlines the necessity for building robust emergency algorithms tailored to gynecological oncology patients in the future.
Evaluation of cardiotoxicity related to cancer treatment in an urban safety-net hospital.
Authors: Michelle Jeung-Eun Lee, Eric Chang, Anekwe Onwuanyi, Sanjay R. Jain
Journal: Journal of Clinical Oncology (2021)

e18804 Background: Improvements in survival of cancer patients has led to an increased awareness of the long-term cardiac effects of chemotherapy. American Society of Clinical Oncology (ASCO) Clinical Practice Guideline emphasizes the needs of identifying patients with higher risk for cardiovascular toxicity prior to treatment initiation. African American (AA) race has been associated with higher incidence of cardiotoxicity and resultant incomplete adjuvant therapy compared to white patients. Here, we investigate the utilization of various imaging modalities to monitor chemotherapy-induced cardiotoxicity in a predominantly AA breast cancer population at the safety-net hospital. Methods: This study was a retrospective analysis of breast cancer patients (n = 33) who received trastuzumab, doxorubicin, and/or paclitaxel between year 2018 and 2020 at the safety-net hospital in Atlanta, Georgia. Patient demographics, clinical characteristics, pathologic variables as well as utilization of echocardiography, echocardiography with global longitudinal strain (GLS), and multigated acquisition scans (MUGA). Results: The majority of patients were AA female (27/33, 81.8%) and the mean age at diagnosis was 52 ± 13.2 years. 11/33 (33%), 24/33 (72.7%), and 20/33 (33.3%) were treated with trastuzumab, paclitaxel, and doxorubicin respectively. Baseline left ventricular ejection fraction (LVEF) was assessed in 32/33 (96.7%) of patients: MUGA 21/32 (65.6%), echocardiography 10/33 (31.3%), and echocardiography with GLS 1/32 (3.1%). 13/32 (40.6%) patients underwent repeated imaging, with the average time between repeat MUGA and echocardiography being 254.3 and 147 days respectively. LVEF decrease of &gt; 10% was noted in 4 patients with repeat MUGA but in none of the repeat echocardiography group. Only 5 patients had echocardiography with GLS over the study period, of which 2/5 (40%) had a drop in GLS in the setting of normal ejection fraction, consistent with occult LV systolic dysfunction. Conclusions: Our study suggests that African American patients at a safety net hospital receive the equivalent level of cardiac surveillance during cancer treatment. However, GLS imaging is underutilized in the detection of subclinical cardiac dysfunction in breast cancer patients receiving chemotherapy. Larger, long terms prospective studies are needed to assess the implications of abnormal GLS and progression to clinical left ventricular systolic dysfunction in the AA breast cancer population.