tbuckley/cabot-search huggingface dataset:
Results of a BNLI randomized trial of G-CSF dose after cyclophosphamide 1.5g/m(2) for progenitor cell mobilization.
Authors: S J Ings, S Schey, B Hancock, M J Watts, E Vandenberghe, A H Goldstone, T Elston, R Pettengell, S Long, P Smith, D C Linch
Journal: Blood (1999)
The difference of clinicopathological characteristics between pure and mixed invasive micropapillary breast carcinoma from China.
Authors: Rong Wang, Wen-Ming Cao, Xiaojia Wang
Journal: Journal of Clinical Oncology (2018)

e13107 Background: Invasive micropapillary carcinoma (IMPC) is a rare pathologic subtype of breast cancer with a high propensity of lymph node metastases. So far the difference of pathological features between pure and mixed IMPC are not fully understood. Methods: A total of 117 cases of IMPC were included from May 2010 to August 2017 in Zhejiang Cancer Hospital, China, among which 48 cases were pure IMPC and 69 cases were mixed IMPC. The clinical and pathological features of these two groups were elaborately compared. Results: In our study, 48 cases were pure IMPC and the rest 69 cases were mixed IMPC. The pure group had a higher rate of luminal B at 37.5%, while there was a higher rate of luminal A at 44.9% in the mixed group (P = 0.035).The average age at diagnosis of the pure and mixed IMPC were 51.0 versus 50.1 years old, respectively (P > 0.05). The mean tumor size of the pure and mixed IMPC were 3.4 cm and 3.78 cm, respectively (P > 0.05). In addition, there were 54.2% and 52.2% patients at stage III in the pure group and mixed group respectively (P > 0.05).We found 18.8%, 29.2%, 16.7% and 35.4% cases with pure IMPC had 0, 1-3, 4-9 or > 10 metastatic lymph nodes, whereas the data were 26.1%, 26.1%, 29% and 18.8% in mixed IMPC group (P > 0.05). Besides, these two groups showed no statistical difference in vascular invasion, with vascular invasion rate of 80.5% for pure group and 76.4% for mixed group, respectively (P > 0.05). The Ki-67 expression between the two groups had no significant contrast. The 2-year disease-free survival rates of the pure and mixed IMPC were 83.8% and 83.7%, respectively (P > 0.05). Conclusions: Our data showed that pure IMPC displayed a nearly similar clinicopathological behavior to the mixed group. While with regard to the molecular subtype, the pure group showed a higher rate to be luminal B, rather than luminal A in the mixed group. However, we didn't find the DFS difference between the two groups because of short follow-up period.
Refining the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma.
Authors: Ofer Margalit, Ronac Mamtani, Scott Kopetz, Yu-Xiao Yang, Yaacov Richard Lawrence, Samir Abu-Gazala, Kim Anna Reiss, Talia Golan, Naama Halpern, Dan Aderka, Bruce J. Giantonio, Einat Shacham-Shmueli, Ben Boursi
Journal: Journal of Clinical Oncology (2018)

e15686 Background: Current guidelines include the use of adjuvant oxaliplatin in clinical stage II/III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population. Methods: Using the National Cancer Database (2006-2013) we identified 6,868 individuals with clinical stage II/III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery and adjuvant chemotherapy. We used multivariate COX regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage. Results: We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (HR = 0.78, 0.67-0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III (HR = 0.69, 0.57-0.83), and was not observed in patients who progressed from clinical stage II to pathological stage III. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0/I, regardless of their clinical stage. Conclusions: Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease.
Circulating cell free DNA to predict recurrence in uveal melanoma.
Authors: Ryan Michael Weight, Shingo Sato, Marlana M. Orloff, Michael J. Mastrangelo, Takami Sato
Journal: Journal of Clinical Oncology (2016)

9569 Background: Uveal melanoma is the most common primary intraocular malignant tumor in adults. Up to 50% of uveal melanoma patients die of metastasis, usually to the liver. Cell free DNA (cfDNA) provides a commercially available, non-invasive mechanism for monitoring disease activity in malignancy. Recently, studies have investigated cfDNA in uveal melanoma and have demonstrated an association with hepatic metastasis, metastatic volume as well as PFS and OS. It remains unclear if cfDNA can predict recurrent metastatic disease in high-risk uveal melanoma patients. Methods: We conductedan exploratory study of cfDNA following treatment for primary intraocular uveal melanoma. Three cohorts were investigated: high-risk patients ( > 50% estimated recurrence rate) with no clinical evidence of metastatic disease (cohort 1), patients with newly developed metastatic disease of the liver by surveillance MRI (cohort 2), patients with previously established metastatic disease (cohort 3). cfDNA profiles were provided by Guardant360 complete exon sequencing and analyzed for the presence of GNAQ/GNA11 mutations and MYC amplification which represent driver mutations present in > 80% of uveal melanomas. cfDNA was evaluated within 1 week of surveillance imaging studies. Results: Cohort 1 revealed no G-protein/MYC abnormalities by cfDNA (0/32). 34.4% (11/32) of patients in cohort 1 had mutations unrelated to G-protein/MYC. Cohort 2 showed a 10% (1/10) G-protein/MYC detection rate. Cohort 3 showed a G-protein MYC detection rate of 75% (18/24) which approaches the expected mutation rate in uveal melanoma. Interestingly, cfDNA did not detect G-protein/MYC abnormalities in hepatic tumors less than 2.0cm in diameter, regardless of cohort. Conclusions: MRI is a more sensitive screening test than cfDNA for detection of hepatic metastasis in uveal melanoma. cfDNA negative for G-protein/MYC alterations correlates with the absence of clinically detectable disease (100% specificity) and a positive result in the adjuvant setting should prompt further evaluation. This study suggests a detection threshold for cfDNA of > 2.0cm hepatic tumor diameter, which may have implications for the utilization of cfDNA across tumor types.
Phase II trial of WT1 analog peptide vaccine in adults with acute myeloid leukemia (AML) in first complete remission (CR).
Authors: Peter George Maslak, Tao Dao, Yvette Bernal, Suzanne M. Chanel, Rong Zhang, Mark G Frattini, Todd L. Rosenblat, Joseph G Jurcic, Raajit Rampal, Jae Hong Park, Dan Douer, Laura Katz, Andres A Gutierrez, Martin S. Tallman, David A. Scheinberg
Journal: Journal of Clinical Oncology (2016)

7005 Background: An NCI consensus study on prioritization of cancer antigens identified WT1 as the #1 ranked immunotherapy target. We previously reported on the safety, immunogenicity, and prolonged survival following vaccination of AML patients in CR in a pilot study with a multivalent WT1 peptide vaccine, SLS-001 (Maslak et.al., Blood 2010). This vaccine consists of 2 native and 2 heteroclitic WT1 peptides designed to activate CD4+ and/or CD8+T cells. We further conducted a Phase II study investigating SLS-001 in adults with AML in CR1 with RT-PCR measurable WT1 transcript levels. Methods: Patients received 6 vaccinations administered with adjuvants Montanide/GM-CSF over 10 weeks with the potential to receive 6 additional monthly doses if they remained in CR. Clinical endpoints were evaluated according to Cheson et. al.(2003). Immune responses were evaluated at week 12 by T-cell proliferation, gamma interferon secretion (ELISPOT) and WT1 tetramer analysis (HLA A02 pts only). Results: 22 patients (7 males; median age 63, 25-76) were treated. Prognostic risk groups (LeukemiaNet) were: Favorable- 8, Intermediate 1- 7, Intermediate 2- 3, Adverse- 3, Unknown- 1. Fourteen patients completed at least 6 vaccinations while 10 of these received all 12 vaccine doses. Fourteen patients relapsed and 10 have died from disease progression. The vaccine was well tolerated with the most common side effects being Grade I/II injection site reaction (45.5%), fatigue (31.8%) and skin induration (31.8%). Two patients discontinued treatment due to possibly related hypersensitivity reactions. Median leukemia free survival (LFS) was 23.5 mos while the overall survival was 45.5 mos (Data to be updated at time of the meeting). Nine of 14 tested patients had a documented immunologic response in one of the correlative assays. Patients that did not make an immune response had shorter LFS and OS than those who made one. Conclusions: These results suggest that the WT1 vaccine is well tolerated, stimulates a specific immune response to the vaccinating peptides, and is associated with prolonged survival. A pivotal international multicenter randomized study is planned for 2016. Clinical trial information: NCTO1266083.
IMRT combined with concurrent S-1 chemotherapy for locally advanced nasopharyngeal carcinoma: A prospective phase II study.
Authors: Tao Lv, Xiaoshen Wang, YuJie Wang
Journal: Journal of Clinical Oncology (2018)

e18085 Background: Intensity modulated radiation therapy (IMRT) combined with concurrent cisplatin chemotherapy is the standard treatment modality for locally advanced nasopharyngeal cancer (NPC). However, some patients can not tolerate cisplatin associated toxicities such as nephrotoxicity, ototoxicity, severe nausea and vomitting, and hematological toxicity. S-1 was reported to decrease the above mentioned toxicities during concurrent chemoradiotherapy (CCRT) in non-small cell lung cancer. Up to date, knowledge is lacking regarding the combination of S1 and IMRT for NPC. So we carried out this prospective study to explore the toxicities and efficacy of concurrent IMRT and S1 for those NPC patients who can not tolerate cisplatin chemotherapy. Methods: From March 2012 to January 2017,133 patients were enrolled into this study. Among those patients, 101 received two cycles of induction chemotherapy with docetaxel and cisplatin, but had severe nausea and vomitting; the rest 32 patients were aged more than 70. IMRT dose prescription was as follows: 66-70.4Gy to GTV, 57-60.8Gy to CTV1, 54-56Gy to CTV2, given in 30-32 fractions. During the course of IMRT, S1 was given by oral administration at 40mg bid everyday without interruption. Toxicities were recorded every week during treatment and toxicities with the highest grade was included in the final analysis. Results: Toxicities during CCRT were as follows: leucopenia, grade 0(66.2%), grade 1(21.8%), grade 2(11.3%), grade3(0.7%). Anemia, grade0(63.2%), grade1(35.3%), grade2(1.5%). Thrombocytopenia, grade0(74.4%), grade1(24.1%), grade2(1.5%). Mucositis, grade 1 (9.0%), grade 2 (60.9%), and grade 3 (30.1%). Vomitting, grade 0 (28.1%),grade 1 (63.9%), grade 2 (9.0%). No patients were found to have hepatic and renal toxicity during CCRT. With a median follow-up of 38 months, the three-year local control rate and distant metastasis-free survival rate was 92.2% and 83.4%, respectively. Conclusions: IMRT and concurrent S1 chemotherapy were well tolerated for locally advanced NPC. Three-year local control rate and distant metastasis-free survival rate was similar to cisplatin-based studies.
Comparison of the prognostic performance between OncoMasTR and OncotypeDX multigene signatures in hormone receptor-positive, HER2-negative, lymph node-negative breast cancer.
Authors: Catherine Margaret Kelly, John Crown, Niamh Russell, Stephen Barron, Seodhna Lynch, Anthony O'Grady, Katherine Sheehan, Joanna Fay, Verena Amberger-Murphy, Anurati Saha, Tony Loughman, Peter Dynoodt, Bozena Fender, Cesar Lopez Ruiz, Chan-Ju Angel Wang, Desmond O'Leary, Darran O'Connor, William M. Gallagher
Journal: Journal of Clinical Oncology (2018)

12074 Background: Multigene prognostic signatures (MGPS) enable identification of early stage breast cancer (BC) patients requiring less aggressive treatment. OncoMasTR is a new MGPS found via a novel transcriptional network analysis method that identified genes – Master Transcription Regulators (MTRs) – that regulate previously identified prognostic biomarkers. The optimised OncoMasTR signature consisting of just 3 MTRs (OM) and incorporating clinicopathological information (OMclinical) has been clinically validated. We examined OncoMasTR’s prognostic performance alone and in comparison to OncotypeDX. Methods: We measured MTR expression levels by RT-qPCR in tissue from Irish patients (n = 367) enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx) study through Cancer Trials Ireland. OM and OMclinical numeric risk scores and risk category (high or low) were blindly calculated using the OncoMasTR algorithm. OncoMasTR scores and OncotypeDX recurrence scores (RS) were independently compared on measures of risk classification, BC recurrence (all, local and distant), correlation and concordance over 9 years of follow-up. Results: OM (LRχ2= 12.92, p = 0.0003) and OMclinical (LRχ2= 17.21, p < 0.0001) provided more prognostic information than RS (LRχ2= 4.74, p = 0.0294). OM classified 39% of samples as low risk (no local or distant recurrence, 0.0% recurrence) and 61% as high risk (9.0% recurrence; 4.5% local, 4.5% distant). OncotypeDX classified 17.3% of samples as low risk (1.9% recurrence; 1.9% local, 0% distant), 63.3% as intermediate risk (7.0% recurrence; 3.5% local, 3.5% distant), and 19.4% as high risk (8.0% recurrence; 3.2% local, 4.8% distant). There was moderate correlation between OM and RS numeric risk scores (r = 0.46, p < 0.0001) and low concordance between the OM and RS risk categories. Higher correlation and concordance were observed among high risk samples. Conclusions: OM, OMclinical and RS were significantly prognostic for recurrence in TAILORx samples. OM and OMclinical demonstrated exceptional sensitivity by classifying all patients who had any recurrence to the high risk category.
Randomized, double-blind phase 3 study evaluating neoadjuvant platinum-based chemotherapy with perioperative pembrolizumab or placebo in resectable stage IIB or IIIA NSCLC: KEYNOTE-671.
Authors: Hiran C. Fernando, Jing Yang, Geri L Ferraro, Steven M. Keller
Journal: Journal of Clinical Oncology (2018)

TPS8583 Background: Robust and durable antitumor activity was previously demonstrated with pembrolizumab in patients with advanced NSCLC, both as a monotherapy in the first- and second-line settings (in patients with PD-L1 tumor proportion score [TPS] ≥50% and ≥1%, respectively) and when combined with pemetrexed-carboplatin (in patients with nonsquamous histology). KEYNOTE-671 (NCT03425643) is a phase 3 study that evaluates standard neoadjuvant chemotherapy with perioperative pembrolizumab or placebo in early-stage NSCLC. Methods: This international double-blind phase 3 trial enrolls patients aged ≥18 years with previously untreated, resectable stage IIB/IIIA NSCLC, ECOG PS 0–1, and tumor samples for evaluation of PD-L1 expression. Patients are randomized 1:1 to neoadjuvant chemotherapy (cisplatin 75 mg/m2 with gemcitabine 1000 mg/m2 [days 1 and 8; squamous histology] or pemetrexed 500 mg/m2 [nonsquamous histology]) combined with either pembrolizumab 200 mg or placebo Q3W for 4 cycles, followed by surgery, then adjuvant pembrolizumab 200 mg or placebo Q3W for 13 cycles. Randomization is stratified by disease stage, PD-L1 TPS < 50% vs ≥50%, squamous vs nonsquamous, and East Asia vs non-East Asia. Radiographic response is assessed 3 weeks after cycles 2 and 4, and every 12 weeks from adjuvant cycle 1 (RECIST v1.1, blinded independent central review). Disease recurrence/progression is confirmed by biopsy. Adverse events are graded per CTCAE v4.0 or later. Primary endpoints are event-free survival (time from randomization to first of disease/local progression, unresectable tumor, local/distant recurrence, or death) and overall survival (time from randomization to all-cause death). Secondary endpoints are major pathological response (≤10% viable tumor cells in resected primary tumor/lymph nodes), pathological complete response (no residual invasive cancer on H&E stained slides of resected lung specimen/lymph nodes post–neoadjuvant therapy), safety, and patient-reported outcomes. An estimated 786 patients will be enrolled, beginning March 9, 2018. Clinical trial information: NCT03425643.
Abstract A24: Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer
Authors: Nemanja Despot Marjanovic, Sheng Rong Ng, Aviv Regev, Tyler Jacks
Journal: Clinical Cancer Research (2018)

Abstract Small cell lung cancer (SCLC) is one of the most aggressive cancer types, and patients in clinic usually (&amp;gt;60% cases) present with metastasis. Current therapies for SCLC have not changed from 1980, and they include a combination therapy of cisplatin and etoposide. Most patients relapse after initial response, and the 5-year survival for extensive stage SCLC is 2%. One possible explanation for the failure of conventional and targeted therapies in cancers is the cellular heterogeneity that exists within tumors. Thus, understanding phenotypic heterogeneity at the single-cell level can be leveraged to predict mechanisms of resistance, which enables the design of effective combination therapies. In this project, we used as a model system an autochthonous mouse model of human SCLC, in which we deleted p53, RB, and p130. We collected multiple primary tumors, circulating tumor cells (CTC), and lymph node (proximal site) and liver (distant site) metastases from the same mouse, and across different mice. These samples were collected at the stage that should correspond to the limited/extensive stage of human SCLC, which is most commonly seen in clinic. Then we used single-cell RNA-seq (sc-RNAseq) methods to define and understand transcriptional heterogeneity in these samples. Furthermore, we aimed to understand the evolutionary relationships between primary tumors, CTCs, lymph node and liver metastases using different computational approaches such as diffusion maps. Further defining and functionally annotating transcriptional heterogeneity will help us better understand the disease, and find the new Achilles heel for targeting. Note: This abstract was not presented at the conference. Citation Format: Nemanja Despot Marjanovic, Sheng Rong Ng, Aviv Regev, Tyler Jacks. Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A24.
Neglected breast cancer in the Appalachians.
Authors: Ruta Arays, Karen Tran-Harding, Jianrong Wu, Donglin Yan, Eric B. Durbin, Emily Fontenot Marcinkowski, Patrick McGrath, Kelly Hawthorne, Edward H. Romond, Mara D. Chambers, Richard Gibbs, Aju Mathew
Journal: Journal of Clinical Oncology (2018)

e13023 Background: Neglected breast cancer occurs due to delay in seeking care. While this is primarily an issue in developing countries it is also observed in high income countries in regions such as Appalachia. We aim to describe the epidemiology of neglected breast cancers seen in our institution. Methods: A patient with a neglected breast cancer should have signs of advanced breast cancer and had at least a 6 month delay from onset of symptom. Patients with inflammatory breast cancer were excluded. Kentucky Cancer Registry (KCR) was queried to find patients that presented to Markey Cancer Center of the University of Kentucky between 1/1/2010 and 12/30/2016 with a diagnosis of breast cancer and initial consultation notes that had any of the following terms – “ulcer,” “open wound,” “neglected,” “fungating,” “ulcerated,” “eschar,” “necrosed,” “advanced.” IRB approval was obtained. Descriptive statistics were done and survival analysis was done through Kaplan Meier method. Results: Seventy-six patients were initially identified and upon further chart review 41 met the criteria for analysis, of which 18 patients had died from metastatic disease. The median age of our population was 58.1 years (range: 28-77). 75.6% of patients had either a fungating or ulcerated mass at diagnosis. Overall 63.4% had hormone receptor-positive cancer, 45% had HER2-positive cancer and 7% had triple negative disease. Majority of patients presented with Stage IV disease (58.5%) and the rest had stage III disease. Patients who presented with stage III disease had a median progression free survival of 1.9 years. After diagnosis of stage IV disease, patients lived for a median of 1.9 years. Median time of survival from diagnosis of neglected breast cancer was 2.6 years. Conclusions: We observed a high rate of HER2-positive disease among patients with neglected breast cancer. In our single-institution study, the prognosis of patients with neglected breast cancer was observed to be poor. Further studies will focus on surveying patients who are alive, to understand reasons for the delay in seeking care.