tbuckley/cabot-search huggingface dataset:
Minimal residual disease (MRD) status pre- and post- high-dose therapy/autologous stem (HDC/ASCT) cell transplantation for multiple myeloma (MM) in the era of novel agents.
Authors: Adetola Kassim, Jeremy Scott McDuffie, Claudio A Mosse, Bipin N. Savani, John P. Greer, Olalekan O. Oluwole, Stacey Goodman, Brian G. Engelhardt, Wichai Chinratanalab, Annette S Kim, Madan H. Jagasia
Journal: Journal of Clinical Oncology (2013)

8605 Background: MRD assayed by multi-parameter flow cytometer (MFC), has prognostic significance after HDT/ASCT for MM (Paiva et. al. 2008). The frequency of MRD negativity (-) after induction therapy using novel agents such as immunomodulatory drugs like lenalidomide (IMiDs), and proteasome inhibitors like bortezomib, is unknown. The impact of HDT/ASCT on MRD status in this patient group has not been studied. Methods: We performed a retrospective study of all MM patients undergoing HDT/ASCT (January 2010 - December 2012) in our institution. No restrictions on inclusion were made based on the International Myeloma Working Group response criteria. All patients had novel agents as part of their initial induction regimen. Statistical analysis was by SPSS software (V 12.0). MRD status was determined by MFC on bone marrow samples pre- HDC/ASCT [M1] and post- HDC/ASCT (D100 [M2] and I year [M3]). MFC was done with antibodies against CD45, CD19, CD138, CD38, CD20, CD56, and anti-k and l cytoplasmic antibodies. Results: MRD status was available on 91 patients pre-transplant. Of these patients, 80 had MFC recorded at M2 and 17 patients had MFC recorded at M3. Fifty-eight percent were male and 76% were Caucasian. Forty percent received IMiDs, while 60% got proteasome based therapies. Of the 91 patients with MRD pre-HDC/ASCT, 58% (53/91) were MRD (-), and of these patients 89% (41/46) remained MRD (-) at M2. 48 patients were MRD positive (+) pre-HDC/ASCT, 58% (20/34) became MRD (-) at M2. Age, cytogenetic risk, disease stage, number of chemotherapy cycles or immunofixation status had no impact on MRD status. There were only 6 relapses in the cohort, thus the impact of MRD status on progression-free survival could not be studied. Conclusions: Novel agents improve depth of response pre-transplant. HDC/ASCT increases MRD negativity post-transplant. MRD status could aid better timing of HDC/ASCT or adoption of a risk-adapted strategy for high-risk patients. MRD status validation in a prospective cohort is underway at our center (NCT01215344). With future follow-up, the impact of MRD on progression-free survival in the era of novel agents will be determined.
Steroid-free regimen with aprepitant in preventing chemotherapy-induced nausea and vomiting in patients with colorectal cancer receiving FOLFOX chemotherapy: A randomized phase III trial.
Authors: Wenjing Wang, Jiayu Ling, Yue Cai, Jianwei Zhang, Huabin Hu, Shanshan Li, Jian Xiao, Yanhong Deng
Journal: Journal of Clinical Oncology (2017)

TPS820 Background: Addition of aprepitant, an NK1 receptor antagonist to a 5-HT3 receptor antagonist and dexamethasone regimen was shown to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC). Little is known about the efficacy of aprepitant when used without dexamethasone. Dexamethasone is widely used to prevent both acute and delayed nausea and vomiting induced by chemotherapy. However, multi-period use of dexamethasone could be associated with side effect, such as hyperglycemia, dyspepsia and insomnia. This randomized phase III trial studies antiemetic therapy with aprepitant and tropisetron to see how well they work compared to dexamethasone plus tropisetron in preventing chemotherapy-induced nausea and vomiting in patients with colorectal cancer receiving FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) chemotherapy. Methods: This trial is an open-label, single-center, randomized phase 2 study. Eligibility criteria include histologically confirmed colorectal cancer, no prior chemotherapy and scheduled to receive FOLFOX, Age ≥ 18 years, ECOG Performance Status 0, 1 or 2. Up to 298 patient will be enrolled and randomized 1:1 to receive aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 and 3) plus tropisetron (5mg IV of day1) or dexamethasone (10 mg IV on day 1 and 5 mg IV on days 2, 3) plus Tropisetron (5mg IV of day1). The primary objective of this study is complete response defined as no emetic episodes and no use of rescue medication. The second objectives include nausea score, time to first vomiting episode or use of rescue medication, frequency of rescue medication and functional Living Index -Emesis (FLIE). Clinical trial information: NCT02909478.
Characterization of a subset of CD4+ T cells expressing CD161 in cancer patients and healthy individuals
Authors: E. G. Iliopoulou, M. V. Karamouzis, S. A. Perez, A. Ardavanis, C. N. Baxevanis, M. Papamichail, G. Rigatos
Journal: Journal of Clinical Oncology (2006)

20016 Background: CD161 is a glycoprotein expressed in &gt;90% of NK and 25% of T cells in the peripheral blood of healthy individuals. Several NK receptors on T cells infiltrating tumors have been proven to negatively influence their effector function and therefore play a role in tumor escape. In this study, we investigated T cells expressing CD161 in the peripheral blood mononuclear cells (PBMC), tumor infiltrarting lymphocytes (TIL) or malignant effusions (ME) from patients with several types of cancer. Methods: Expression of CD161 in CD4 + or CD8 + (lacking CD56) T cells, was examined using four-colour flow cytometry. The proliferative capacity and potential cytokine production of purified CD4 + CD161 + CD56 − cells, were studied after weak or strong stimulation, with or without costimulation, in the presence or absence of Interleukin-2 (IL-2). The possible regulatory function of activated CD4 + CD161 + CD56 − cells on T cell allo-responses was also investigated. Results: CD4 + CD161 + CD56 − T cells were significantly increased (P &lt; 0.01) in TIL, either from tumor tissue (n = 8) or metastatic lymph nodes (n = 5), and ME (n = 25), compared to PBMC from both cancer patients (n = 36) and healthy individuals (n = 12). CD4 + CD161 + CD56 − cells from all sources tested, have the same phenotypic characteristics: they comprise a memory T cell population (CD45RO + CD45RA − ) expressing high CD28 and CD95 and low CD25, CD38 and HLA-DR. Co-stimulation via CD28 is important for induction of proliferation and production of large amounts of Th1 and Th2 cytokines (IFN-γ, TNF-a, GM-CSF, IL-4 and IL-10). Following co-stimulation, CD4 + CD161 + CD56 − cells also exert a suppressive activity on autologous PBMC allo-responses. The latter effect does not require cell-to-cell contact and is mediated by soluble factors, including IL10, since neutralization of IL10 partially restored the immune response. Conclusions: CD4 + CD161 + CD56 − cells represent a distinct memory T cell population that is significantly increased in TIL and ME in patients with cancer. These cells are capable of secreting large amounts of both Th1 and Th2 cytokines and might play an immunosuppressive role, mainly through IL-10 production, depending on the microenvironment in which they develop. No significant financial relationships to disclose.
Mechanisms of primary AI resistance in ER-positive HER2-negative breast cancer.
Authors: Daishu Miura, Tsuguo Iwatani, Hidetaka Kawabata
Journal: Journal of Clinical Oncology (2013)

e11519 Background: Current approaches of neoadjuvant endocrine therapy (NAET) are focusing on biomarker analysis of the diagnostic specimens however inadequate response occurs in 5-10% of patients treated. It has been reported hormone resistance may predict Ki67 level after treatment than ΔKi67. Much less is known about the difference between Ki67 increases and still high level of Ki67 after NAET. A pilot study was conducted to investigate the differences of biomarker changes in short-term NAET (letrozole vs. exemestane). Differences of resistant mechanisms between Ki67 increases and Ki67 still high expression and between two AIs were studied. Methods: Totally 116 samples from 58 postmenopausal women with ER positive HER2 negative stage 1-3 breast cancers comparing LET and EXE were analyzed with pre- and post-treatment mRNA expression of multiple biomarkers using QuantiGene Assay. Each of 29 patients took LET or EXE until the surgery (median 22 days). Compared with Ki67 expression of pre/post treatment, we classified resistance into 2 groups, Ki67 increase after treatment (INC) or Ki67 still high expression (equivalent over 14% in IHC) except those in INC (HIG). Results: Clinical characteristics were well balanced between the two treatment arms. Median % changes of Ki67 were -59% in both LET and EXE. Six cases (10%) were in INC (3/LET and 3/EXE). Among 10 cases of still high Ki67 expression, 6 (10%) were in HIG except 4 cases of Ki67 increases (3/LET and 3/EXE). All 6 cases in INC had increases of ERβ, MAPK, PIK3CA, ALDH1, NFkB, and RANKL and decrease of ERα. Five out of 6 in INC had an increase of HER2 and a decrease of PR. While changes in HIG were various, a nonsignificant trend to predict resistance was found. However all 3 cases whose HER2 increased in HIG had also increases of MAPK and PIK3CA. All 3 receiving EXE had increases of PR. Conclusions: Although both LET and EXE had significant decreases of Ki67, no significant difference was found between two. Both had 20% of primary resistance in terms of Ki67. Tumors which Ki67 increase seem to activate various signaling pathway, which mechanism is class effect of AI. What Ki67 is still high supposed to be nonclass effect.
Continuous low-flow ascites drainage and sequential non-invasive tumor-cell sampling through the urinary bladder via the alfa-pump closed system in platinum-resistant ovarian cancer (PROC): First clinical experience in a cancer patient.
Authors: Christina Fotopoulou, Laura Spiers, Emily Pickford, Roberto Dina, Sarah Patricia Blagden, Nagy A Habib, Hani Gabra
Journal: Journal of Clinical Oncology (2013)

5562 Background: Malignant ascites in PROC causes significant impairment in quality of life. The Sequana Medical alfapump System (AP), a remotely controlled device connecting the patients’ peritoneal cavity to their urinary bladder, has been evaluated for the continuous drainage of ascites in liver cirrhosis, but not as yet for malignant ascites. Methods: We implanted the AP in the peritoneal cavity of a 67y old heavily pretreated PROC patient with recurrent malignant ascites requiring 3-5 liters drained 3 times/month. The AP was evaluated for its ability to drain ascites into the urinary bladder using an electronic download of recorded volume pumped, cross correlated with weekly ultrasound, symptomatic scores and QoL evaluation. Early morning urine for evaluation of urinary cytology and tumor-cell molecular analysis was collected weekly. Results: The implantation was performed under general anaesthesia in a 60 minute procedure. Before insertion the patient had 3 liters of malignant ascites; 2 liters were drained during surgery. The pump, draining 350ml ascites per day successfully drained the ascites to dryness after 3 days. The patient underwent weekly sonography and monthly cystoscopies. She did not report pollaki- or dysuria, only an increased micturition volume. Histopathological analysis of the urine revealed rich malignant cell content, used to create FFPE cell blocks weekly for molecular- pathological profiling with sequential Caris Target Now analysis and full exome sequencing. Conclusions: On initial evaluation, the AP represents a tolerable and effective means of diverting peritoneal ascites into the urinary bladder and thus preventing its recumulation in PROC. This innovative approach not only addresses an area of unmet need for the control of malignant ascites but also provides a method of collecting tumor tissue and evaluating longitudinal change in molecular tumor characterization. A EUTROC multicenter European randomized trial (AMAZE) is planned for evaluation of clinical and translational implications of the AP in PROC.
Prediction of metastatic behavior in high-grade pleomorphic soft tissue sarcomas by gene expression.
Authors: Keith M. Skubitz, Amy Skubitz, Wayne Xu, Xianghua Luo, Pauline Lagarde, Jean-Michel Coindre, Fred Chibon
Journal: Journal of Clinical Oncology (2013)

10561 Background: The biologic heterogeneity of soft tissue sarcomas (STS) complicates treatment. Metastatic propensity may be determined by gene expression patterns that do not correlate well with morphology. In earlier studies, gene expression patterns were identified that distinguish 2 subsets of clear cell renal carcinoma (RCC), serous ovarian carcinoma (OVCA), and aggressive fibromatosis (AF). We reported the use of a gene set derived from these three studies to separate 73 high grade STS into groups with different probabilities of developing metastatic disease (PrMet). We wished to confirm our findings using an independent data set. Methods: We utilized these gene sets, hierarchical clustering (HC), Kaplan-Meier, and log-rank analyses to examine the Affymetrix HU_133 expression profiles of 309 STS. Results: HC using a pooled gene set derived from the AF-, RCC-, and OVCA-gene sets identified subsets of the STS samples. Kaplan-Meier analysis revealed differences in PrMet between the clusters defined by the first branch point of the clustering dendrogram (p=0.048), and also among the 4 different clusters defined by the second branch points (p&lt;0.0001). Analysis also revealed differences in PrMet between the leiomyosarcomas (LMS), dedifferentiated liposarcomas (LipoD), and undifferentiated pleomorphic sarcomas (UDS) (p=0.0004). HC of the LipoD and UDS samples with the pooled probe set divided the samples into 2 groups with different PrMet (p=0.013, and 0.0002, respectively). HC of the UDS samples also showed 4 groups with different PrMet (p=0.0007). In contrast, HC found no subgroups of the LMS samples. Each individual gene set (AF-, RCC-, and OVCA-) separated the UDS samples into subsets of different metastatic outcome, but only the AF- gene set separated the LipoD samples, and no gene set identified LMS subsets. Conclusions: These data confirm our earlier studies and suggest that this approach may allow the identification of more than 2 subsets of high grade STS, each with distinct clinical behavior, and may be useful to stratify STS in clinical trials and in patient management.
Cancer rehabilitation outpatient consultation: Patient characteristics, symptom burden and quality of life.
Authors: Carolina Gutierrez
Journal: Journal of Clinical Oncology (2017)

136 Background: Cancer rehabilitation focuses on the functional and psychological needs of cancer survivors. Patient-reported outcomes have been increasingly used as part of the standard of care during clinical encounters. We review characteristics that patients present to their outpatient cancer rehabilitation consultation at a large academic hospital. Methods: Patients presenting for their first outpatient cancer rehabilitation consultation completed a paper copy of the PROMIS-10 (Patient Reported Outcomes Measurement Information System) instrument immediately prior to meeting with the physician. It includes 10 items evaluating quality of life, social life, functional activity, mental health, pain, and fatigue. A caregiver or health care provider could provide assistance in completing the form. Patient-reported outcomes were analyzed as part of an IRB-approved protocol. Data were analyzed using descriptive statistics and the “PROMIS Scoring Global Short Form v1.0 and v1.1” (12/16/2010). T-Score distributions are standardized such that a 50 represents the average (mean) for the US general population, and the standard deviation around that mean is 10 points. Results: Twenty-seven patients presented for consultation (63% women, 37% men) from 3/2014 through 6/2015 with an average age of 54.5 (44-76 range). Disease types included 52% brain tumors, 33% breast, 5% prostate, and 1% of each of the following: melanoma, myelofibrosis, and multiple myeloma. For our population, the physical health subscale score was 11.51 with a T-Score 38.6, standard error 4.1, a T-Score more than one standard deviation below the population mean. The mental health subscale was 11.92 with a T-Score 43.5, standard error 3.6, representing less than one standard deviation below the mean. The global health score was 28.55, which fell 2 standard deviations below the population mean. Conclusions: Compared to the US population mean, cancer survivors presenting for a cancer rehabilitation consultation had lower physical health than mental health. Our findings suggest the importance of screening cancer survivors for physical impairments and providing interventions focused on functional recovery.
Safety, tolerability, and pharmacokinetics (PK) of rilotumumab (R) combined with cisplatin (C) and capecitabine (X) in Japanese patients (pts) with MET-positive metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: Toshihiko Doi, Kensei Yamaguchi, Yoshito Komatsu, Kei Muro, Tomohiro Nishina, Takako Eguchi Nakajima, Richard Lizambri, Elwyn Loh, Rui Tang, Yilong Zhang, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2014)

4051 Background: R is an investigational, fully human monoclonal antibody to hepatocyte growth factor, the MET receptor ligand. This study assessed the safety, PK, and tumor response of R + CX in Japanese pts with MET-positive G/GEJ cancer. Methods: An initial cohort evaluating dose-limiting toxicities (DLTs) is described; an expansion cohort has fully enrolled and will be reported. Eligible pts were Japanese, age ≥20 years, ECOG ≤1, and had pathologically confirmed MET-positive unresectable, locally advanced/metastatic G/GEJ adenocarcinoma. In each 21-day cycle, pts received R 15 mg/kg IV (day 1), C 80 mg/m2 IV (day 1; up to 6 cycles), and X 1000 mg/m2 BID orally (days 1−14). Endpoints included DLTs, adverse events (AEs), PK of R and CX, and objective response. Results: The initial cohort enrolled 6 pts; there was 1 DLT (grade 3 decreased appetite). All pts had treatment-emergent AEs (TEAEs). TEAEs occurring in >3 pts were decreased appetite (n=5), nausea (n=5), fatigue (n=4), and palmar-plantar erythrodysesthesia (n=4). Three pts had grade ≥3 TEAEs (diarrhea and neutropenia [n=2 each]; decreased appetite, hypoalbuminemia, hypocalcemia, hyponatremia, hypophosphatemia, leukopenia, and stomatitis [n=1 each]). Grade ≥3 treatment-related AEs (TRAEs) were diarrhea (n=2), neutropenia (n=2), decreased appetite, leukopenia, and stomatitis (n=1 each). There was 1 grade 4 TRAE (neutropenia). One pt discontinued R due to nonserious arterial thrombosis. There were no life-threatening or fatal R-related AEs. The mean end-of-infusion concentrations of R were 212, 275 and 272 μg/mL in cycles 1, 2 and 3, respectively. Exposures to CX were similar across cycles. The mean Cmax of X and its metabolite 5-FU was 6.1 and 0.3 μg/mL. The mean Cmax of total and unbound C was 3.8 and 1.4 μg/mL. The mean t1/2was 0.5, 0.7, and 12.3 h for X, 5-FU, and unbound C. Two pts had a partial response. Conclusions: The toxicity profile of R + CX in Japanese pts with MET-positive G/GEJ cancer was consistent with that of Western pts. Safety and PK results support further evaluation of R + chemotherapy in MET-positive G/GEJ cancer. Clinical trial information: NCT01791374.
Duloxetine in symptomatic chemotherapy-induced peripheral neuropathy: Single-center experience beyond the clinical trial.
Authors: Roser Velasco, Cristina Santos, Roso Sala, Marta Simo, Cristina Izquierdo, Miguel J. Gil Gil, Laura Jimenez, Beatriz Pardo, MaCarmen Galan, Ramon Palmero, Ramon Salazar, Jordi Bruna
Journal: Journal of Clinical Oncology (2015)

e20713 Background: Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is the only agent demonstrated effective in treating pain related with chemotherapy induced peripheral neuropathy (CIPN). The phase III randomized, double-blind, placebo-controlled trial published in 2013 showed a moderate effect on CIPN pain relief, becoming the first choice. Methods: Single-institution consecutive cancer patients with CIPN treated with duloxetine during the year 2014 were prospectively collected. Aim of the study was to evaluate the drug's efficacy, rate of compliance and adverse-effects profile. Only patients with chronic symptomatic CIPN, non-progressive disease and two follow-up visits were included. CIPN was graded employing the Total Neuropathy Score and NCI.CTC v4. Response to duloxetine was assessed with patient global impression of change (PIGC) scale (1: no benefit; 7: excellent response). Results: 73 patients were analyzed. 39 (53%) were women. Median age was 61 (29-81). 51 and 20 patients received platinum and taxane-based regimen, respectively, for colorectal (n = 40), breast (n = 17), germinal (n = 5), gynecological (n = 3), lung (n = 1), gastric (n = 2), and other (n = 5) cancer. Median TNS was 9 (1-17). Severity of CIPN was grade 1 (12%), grade 2 (49%) and grade 3 (12%). 45 (61.6%) patients discontinued duloxetine treatment due to side-effects (38%) or ineffectiveness (23%). No differences on rates of stopping treatment due to side-effects were observed between gender. Discontinuation due to perception of ineffectiveness was more frequently reported by men (37.1% vs 10.5%, p = 0.005). Women presented higher punctuations on PIGC scale compared with men (3.8 ±2.1 vs 1.94 ±1.8, p = 0.005) and were more probable that continue treatment (20% vs 34.2%, p = 0.022). No significant differences according CIPN severity neither type of chemotherapy were observed in drop-out and retention rates. Conclusions: More than one-third of all patients stop duloxetine early due to intolerable side-effects, a rate three times higher than reported. Among treated, women population seems to experiment more benefit. Low tolerability and male gender may limit duloxetine usefulness in symptomatic CIPN.
Intestinal dendritic cell licensing through Toll-like receptor 4 is required for oral tolerance in allergic contact dermatitis
Authors: Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
Journal: Journal of Allergy and Clinical Immunology (2017)