tbuckley/cabot-search huggingface dataset:
First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.
Authors: Rouslan Kotchetkov, David Susman, Lauren Gerard, Erica DiMaria, Derek Wayne Nay
Journal: Journal of Clinical Oncology (2021)

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m 2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m 2 . A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.
Dedifferentiated chondrosarcoma: A report of the clinicopathologic features and outcomes of 16 cases treated at a single institution.
Authors: Charles Gusho, Steven Gitelis, Alan T. Blank
Journal: Journal of Clinical Oncology (2021)

e23500 Background: Dedifferentiated chondrosarcoma (DCS) is a rare and aggressive malignancy with a poor prognosis. The purpose of this investigation was to assess the clinicopathological features and outcomes of DCS patients treated at a single institution. Methods: This study was a retrospective review over a consecutive twenty-year period. Data including treatment details and outcomes were recorded. Results: A total of 16 cases from 2000 to 2018 were reviewed. The median age was 62 years (IQR, 52-69 years) and the majority of DCS arose in the femur (50%, n = 8) and pelvis (25%, n = 4). Fourteen (88%) cases received limb salvage/wide margin resection (n = 13) or intralesional surgery (n = 1). For all DCS, the median estimated overall survival (OS) was 46 months (95% CI, 1-90 months) with both a five and ten-year survival probability of 32%. On Kaplan-Meier analysis there was no difference between operative versus nonoperative management (p = 0.747), surgery alone versus surgery/chemotherapy (p = 0.265), nor surgery alone versus surgery/chemotherapy/radiation (p = 0.698). Conclusions: Our findings confirm the poor prognosis of DCS patients, though with a five-year estimate of 32%, higher than previous literature. Together with existing literature, our data may enable future strategic recommendation of DCS patients.
Phase I study of LZM005, a HER2 antibody, as monotherapy or in combination with trastuzumab and docetaxel in patients with HER2-positive metastatic breast cancer.
Authors: Cong Xue, Herui Yao, Ying Lin, Xin An, Meiting Chen, Yugang Dong, Su Li, Yanxia Shi
Journal: Journal of Clinical Oncology (2021)

1042 Background: LZM005 is a novel anti-HER2 antibody that binds with elevated affinity to the domain II of HER2. This phase I study assessed the safety, tolerability, pharmacokinetics (PK) and activity of LZM005, as monotherapy or combined with trastuzumab and docetaxel in patients with HER2-positive metastatic breast cancer. Methods: The phase I trial included phase Ia and Ib. Phase Ia was the monotherapy dosage escalation design. LZM005 was administered intravenously with 5mg/kg, 10mg/kg, 15mg/kg and 20mg/kg. The endpoints were dose limited toxicity (DLT) and maximum-tolerated dose (MTD), safety, tolerability and PK analysis. In phase Ib, LZM005 was combined with trastuzumab and docetaxel with MTD. The endpoints included safety and tolerability, response, PK and biomarker analysis. Results: From Jan 2017 to Feb 2020, 35 patients received LZM005 (15 monotherapy, 20 combination). No DLT was observed from 5mg/kg to 20mg/kg. In phase Ib two arms were set: 420mg arm and 525mg arm. The pharmacokinetics of LZM005 were similar to pertuzumab (Table). Common adverse events included increased transaminases, diarrhea and anemia in monotherapy and combination therapy. The common AE in phase Ia trial included diarrhea (21.4%), anemia (14.3%), elevated transaminase (14.3%). The common AE in phase Ib trial included anemia (44.1%), diarrhea (41.2%), fatigue (26.5%), elevated transaminases (23.5%), nausea (20.6%), rash (17.6%) and asymptomatic urinary tract infection (11.7%). All adverse events were manageable. No treatment-related death occurred. The clinical benefit rate and objective response rate was respectively 42.90% (6/14) and 7.14% (1/14) with monotherapy, with combination cohort was 100% (8/8) and 62.5% (5/8) in trastuzumab-naive, 83.3% (11/12) and 41.7% (5/12) in trastuzumab-pretreated patients. The median progression free survival was 22.5 weeks. Conclusions: LZM005 was well tolerated and showed potent activity in patients with HER2-positive metastatic breast cancer. Further evaluation was warranted. Clinical trial information: CTR20191921 .[Table: see text]
Clinical validation of EndoPredict in premenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer.
Authors: Anastasia Constantinidou, Yiola Marcou, Timothy Simmons, Ryan Bernhisel, Elisha Hughes, Stephanie Meek, Eleni I. Kakouri, Georgios Georgiou, Ioanna Zouvani, Gabriella Savvidou, Vanessa Kuhl, Jennifer Doedt, Susanne Wagner, Alexander Gutin, Jerry Lanchbury, Ralf Kronenwett, Emad A. Rakha
Journal: Journal of Clinical Oncology (2021)

537 Background: The EndoPredict 12-gene prognostic assay is validated to predict distant recurrence-free survival (DRFS) and response to chemotherapy in post-menopausal women with ER+, HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women. Methods: Stored tumor samples from women with ER+, HER2- primary breast cancer who were pre-menopausal at the time of diagnosis and were systemically treated with endocrine therapy alone were obtained from two sites (University of Nottingham and University of Cyprus). These samples were tested with EndoPredict to produce a 12-gene molecular score (EP). Pathologic tumor size and nodal status were algorithmically combined with the EP score to produce the clinicomolecular EPclin score. Cases with tumors &gt; pT3, which were treated with chemotherapy, or for whom the EPclin score was missing or invalid were excluded. Associations of EP and EPclin with 10-year DRFS were evaluated in terms of hazard ratios (HRs) from Cox proportional hazards models stratified by cohort. 10-year DRFS was estimated for EPclin high-risk and low-risk women by Kaplan-Meier analysis. Results: Out of 411 eligible cases, 385 had a valid EPclin score and were included in the analysis. Mean age at breast cancer diagnosis was 46.5 years (standard deviation 4.7). Most women (N = 239, 62.6%) had grade II tumors and 16.1% (N = 62) had node-positive disease. Over the observation period (median 9.7 years, interquartile range 6.6-13.9 years), 35 women had a distant recurrence within 10 years. Both the molecular EP score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR 1.3, 95% confidence interval (CI) 1.2-1.5; p &lt; 0.001 and HR 3.6, 95% CI 2.3-5.7; p &lt; 0.001, respectively]. Of these patients, 249 (64.7%) were categorized as low risk by EPclin score while the remaining 136 (35.3%) were categorized as high risk. Compared to EPclin low-risk women, EPclin high-risk patients were more likely to experience distant recurrence (HR 4.6, 95% CI 1.4-15.2; p = 0.004). At 10 years post-diagnosis, EPclin low-risk women who received endocrine therapy alone had a DRFS of 97% (95% CI 93-99%). Conversely, EPclin high-risk women had a DRFS of only 76% (95% CI 67-82%). Conclusions: The EPclin score is highly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. Based on these data, pre-menopausal women with EPclin low-risk breast cancer may safely forgo adjuvant chemotherapy in addition to endocrine therapy.
Feasibility of using data collected through the St. Jude Pediatric Oncology Facility integrated local evaluation (PrOFILE) tool to determine previously defined levels of pediatric hematology-oncology care.
Authors: Aniekan Udoko, Pedro Mazotti-Roso, Enrico Suriano, Fernando Silva-Perez, Heather Forrest, Madison Bass, Miriam Gonzalez-Guzman, Paola Friedrich
Journal: Journal of Clinical Oncology (2021)

e13530 Background: Pediatric hematology and oncology (PHO) facilities are not all equally equipped to diagnose and treat the full range of childhood cancers. Proposed facility tier models have been published to facilitate the context-based adaptation of PHO diagnostic and treatment guidelines. However, a tool to assist facilities in identifying their level of PHO care does not exist. We assessed the feasibility of using the St. Jude Pediatric Oncology Facility Integrated Local Evaluation (PrOFILE) tool to identify (1) facility levels as defined by the International Society of Pediatric Oncology (SIOP) and the Lancet Oncology Commission (LOC) for sustainable care for children with cancer, and (2) treatment strata in the Adapted Resource and Implementation Application (ARIA) Guide. Methods: This study employed a multi-step mapping approach. We mapped the 1,279 PrOFILE tool variables to the nine SIOP service lines, ten LOC domains, and ten ARIA resource groups. Mapping was performed by two teams and carried out in two different rounds. The first round aimed to define if an indicator was fully or partially covered by PrOFILE. Multiple PrOFILE variables could be assigned to each concept to meet its content specificity. Various cut-offs were applied when necessary to assign mutually exclusive responses to each tier. The second round consisted of expert validation for each indicator previously identified. Results: Most (97%) of SIOP’s indicators were partially or fully covered in the PrOFILE tool (Table). Radiation therapy tools and appointment scheduling and call back system could not be mapped. Of the LOC indicators, 89% were covered (Table). Pathology technical staff, chemotherapy complexity (low, moderate, and high), lymph node biopsy, organ preservation, liver transplantation, intensity-modulated radiotherapy, and research infrastructure could not be mapped. Finally, 77% of the indicators used by the ARIA Guide were covered (Table). The ophthalmology resource group could not be fully mapped. Conclusions: This exercise demonstrates the feasibility of using PrOFILE tool variables to identify facility PHO care levels as defined by SIOP and LOC. The tool also contains most of the variables necessary to apply the ARIA Guide to diagnose, treat, and manage childhood cancer. Future PrOFILE versions will address concepts that are not covered or are partially covered in its current version.[Table: see text]
Abstract 15828: Alx-0081, a Selective Inhibitor of the Interaction Between Platelet Gpib and Von Willebrand Factor, Prevents Ischemic Stroke in the Guinea Pig: Comparison With the Thrombolytic Rtpa.
Authors: Stefania Momi, Michela Tantucci, Maarten Van Roy, Hans Ulrichts, Josefin Holz, Paolo Gresele
Journal: Circulation (2010)

The interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (VWF) triggers the initial step of platelet adhesion and arterial thrombus formation. Antiplatelet therapy is the c...
Can patients with advanced malignancy and poor performance status benefit from nivolumab plus ipilimumab as a palliative treatment?
Authors: Omar Khaled Abughanimeh, Smriti Sharma, Robin High, Mridula Krishnan, Benjamin A. Teply
Journal: Journal of Clinical Oncology (2021)

12028 Background: Performance status (e.g. Eastern Cooperative Oncology Group [ECOG] score) is a predictive tool used to determine whether a patient may benefit from cytotoxic chemotherapy. The toxicity profile of immunotherapy is different, and less is known about whether performance status (PS) is similarly associated with toxicity and benefit. Nonetheless, most clinical trials for immune checkpoint inhibitors have excluded patients with poor PS. Emerging data by our group and others has linked poor PS with lack of response and decreased survival with anti-PD-1/L1 agents, but whether combination therapy abrogates the poor outcomes of PD1 only therapy is unknown. Methods: We conducted a retrospective cohort study of patients with metastatic cancer who received ipilimumab plus nivolumab at our institution between January 2014-December 2020. We compared outcomes between those with good PS (Group A, ECOG PS 0-1) and poor PS (Group B, ECOG PS ≥ 2). Our primary outcomes were overall survival (OS) and incidence of grade 3-4 immune-related adverse events (irAEs). Other outcomes included objective response rates and need for hospitalization. We utilized the Kaplan-Meyer method for time to survival analysis and exact Pearson Chi-squared testing for response, toxicity, and hospitalization analysis. Results: A total of 129 patients were identified with a mean age of 59.9 years. Among them were 73 males (57%) and 56 females (43%). Malignant melanoma was the most common malignancy (39%) followed by renal cell carcinoma (27%), small cell lung cancers (10%), non-small cell lung cancers (9%), and the rest with other histologies. 113 patients (87.6%) were in group A and 16 (12.4%) in group B. Across all tumor types, patients in Group B had significantly worse OS compared to group A (HR 0.24 [0.13-0.48], P = &lt; 0.0001). Group B similarly had higher rates of hospitalization compared to group A (94% vs 56%, P = 0.0048). Interestingly, irAEs were not driving these hospitalizations, with a trend toward lower rates of irAEs in the poor PS group (19% vs 46% in Group A, P = 0.057). The overall response rate in group B was numerically lower (6% vs 26% in group A, p = 0.1). Conclusions: Our study showed that using ipilimumab plus nivolumab in patients with poor PS was associated with significantly poorer OS and higher rates of hospitalizations. irAEs were not increased in the poor PS group, suggesting a lack of treatment efficacy seemed to driving these poor outcomes. Extrapolation of clinical trial data for ipilimumab-nivolumab to a broader population including those with poor PS should be done with caution. Unfortunately, our data showed that most patients with poor PS were not adequately palliated with ipilimumab-nivolumab.
Racial disparities among women who develop invasive secondary breast cancer.
Authors: Kekoa Taparra, Jami Aya Fukui, Jeffrey Killeen, Kenneth N. M. Sumida, Lenora Loo, Brenda Y Hernandez
Journal: Journal of Clinical Oncology (2021)

e18523 Background: Noninvasive breast cancers ( e.g. ductal and lobular carcinoma in situ) are highly treatable nonobligate precursors to invasive breast cancers. However, even after treatment, some women develop second breast cancers (SBCs), increasing their mortality risk. Prognosticators may inform treatment recommendations for women at higher risk of SBC. In this study, risk factors for SBC were evaluated using deidentified data from the Hawaiʻi Tumor Registry (HTR), an NCI SEER registry. The HTR covers a uniquely multiethnic, statewide population allowing for elucidation of disparities in understudied U.S. populations. Methods: Women initially diagnosed between 1973-2017 with noninvasive (ductal and lobular) breast cancer were identified. Patient demographics, cancer characteristics, and treatment information were collected. Univariate (UVA) and multivariate (MVA) logistic regression analyses were used to identify factors associated with SBC, defined as a breast cancer diagnosis &gt; 6 months after their prior cancer. Results: Of 7,057 women diagnosed with a first noninvasive breast cancer, 696 (10%) developed SBC. Invasive ipsilateral (iiSBC) and invasive contralateral (icSBC) disease represented 9% and 20% of patients who developed SBC, respectively. The five most prevalent ethnic groups were Chinese, Filipino, Japanese, Native Hawaiian, and White. When adjusting for confounders, women who developed iiSBC were more likely to be Native Hawaiian (odds ratio [OR] = 3.20, 95% CI = 2.07-4.94) or Filipino (OR = 1.72, 95%CI = 1.02-2.91) when compared to Whites; diagnosed between 1990-1999 (OR = 2.06, 95%CI = 1.27-3.34); and not have undergone surgical treatment (OR = 2.93, 95%CI = 1.42-6.04). Women who developed iiSBC were less likely to be &gt; 50 years old (OR = 0.67, 95%CI = 0.49-0.90); diagnosed between 2010-2017 (OR = 0.18, 95%CI = 0.09-0.35); received lumpectomy with radiation therapy (OR = 0.54, 95%CI = 0.35-0.72); and undergone mastectomy (OR = 0.48, 95%CI = 0.32-0.72). Women who developed an icSBC were more likely to be Native Hawaiian (OR = 1.58, 95%CI = 1.06-2.35) or Filipino (OR = 1.60, 95%CI = 1.06-2.42). These women were also less likely to have been diagnosed between 2010-2017 (OR = 0.30, 95%CI = 0.17-0.53). On a subset analysis separating all patients with SBC by first course treatment type, there were no statistically significant differences for treatment type based on race/ethnicity. Conclusions: Overall, in this observational study, Native Hawaiian women, Filipino women, and younger women had increased odds of developing invasive SBC. This study highlights racial disparities in SBC development risk that was not previously appreciated among disaggregated groups of Pacific Islanders and Asian women when compared to White women. This may help oncologists understand the risk of developing SBC in these understudied populations.
Use of circulating tumor DNA in colorectal cancer patients to assess tumor burden and response to therapy: An observational study.
Authors: Erin L. Symonds, Susanne Kartin Pedersen, Bernita Hui Li Yeo, Hiba Al Naji, Susan E. Byrne, Amitesh Chandra Roy, Graeme P. Young
Journal: Journal of Clinical Oncology (2021)

3528 Background: Residual disease after treatment for colorectal cancer (CRC) poses a risk for recurrence but imaging and CEA are limited in their capacity to detect residual disease. A simple test is needed for assessing treatment response. This study determined whether levels of methylated BCAT1/IKZF1 DNA in blood correlate with tumor burden and whether post-treatment levels inform efficacy of different treatments for CRC. Methods: Patients with primary CRC had blood collected prior to treatment (n = 282, 59.9% males, median age 68.5y). Cell free DNA (cfDNA) was extracted from plasma and assayed for methylation in BCAT1 and IKZF1. Detection of methylation in either gene deemed a sample positive; levels were expressed as %methylation (average methylation/average cfDNA). Positive patients had additional samples collected post-treatment for early stage CRC (surgery, n = 31), advanced/metastatic CRC (surgery + adjuvant chemotherapy, n = 15), and rectal cancer (neoadjuvant therapy, surgery +/- chemotherapy, n = 6), or following mid-therapy suspension of treatment in advanced CRC (n = 24). Tumor size was expressed as the maximum diameter of the primary (assessed surgically or by MRI). Results: Pretreatment results increased with CRC stage. Positivity by stage was: I, 23.7% (14/59); II, 62.1% (54/87); III, 68.6% (70/102); IV, 85.3% (29/34). Level by stage: I, 0.0%; II, 0.06%; III, 0.07%; IV, 4.07%, p &lt; 0.001). Pretreatment levels correlated significantly with tumor size (r = 0.372, p &lt; 0.001). Post-treatment blood was collected a median 2.4mo (IQR 1.7-3.9) after therapy completion. Positivity decreased after completing treatment (Table), with 88.4% of cases (46/52) becoming ctDNA negative. All cases with complete treatment had a reduction in biomarker levels, whereas in those with incomplete therapy, 54.5% (12/22) remained positive and the pre- and post-treatment levels were not significantly different. Of those positive after treatment, 13 had a further blood sample: 8 had become ctDNA negative and all but one remained disease free. Five remained positive and all had further suspected or confirmed disease. Conclusions: Levels of methylated BCAT1 and IKZF1 DNA in blood correlated with tumor burden; levels became undetectable in the majority of patients following completion of planned curative intent treatment. The methylated ctDNA blood test aids monitoring of responses to therapy and identification of those cases with residual cancer who might benefit from ongoing therapy.[Table: see text]