tbuckley/cabot-search huggingface dataset:
Hypogammaglobulinemia increases the risk of chemotherapy associated febrile neutropenia in patients with chronic lymphocytic leukemia
Authors: C. Huang, S. Taylor, N. S. Majhail, M. Pabla, A. Malani, J. Singh
Journal: Journal of Clinical Oncology (2006)

18549 Background: Infections are the major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). Hypogammaglobulinemia, in general, increases the susceptibility to infections in patients with CLL. We conducted a case-control study to investigate whether hypogammaglobulinemia (Immunoglobulin-G (IgG) level &lt;600 mg/dL) increases the risk of febrile neutropenic episodes in CLL patients with chemotherapy associated neutropenia (absolute neutrophil count (ANC) &lt;0.5 × 109/L). Methods: The source cohort consisted of all consecutive patients with CLL seen at our institution between Jan 2002 to June 2005.We identified 8 cases of chemotherapy associated febrile neutropenia; controls consisted of 18 patients, with neutropenia but no fever (n = 4) or no neutropenia (n = 14). Results: The two groups were comparable except for a higher proportion of patients with Rai stage-4 disease in the febrile neutropenia cohort (100% vs. 17%, p &lt; 0.001). Eight of the 8 patients in febrile neutropenia group were found to be hypogammaglobulinemic as compared to 2 of 18 controls (100% vs 11%, P value &lt; 0.001). The median IgG level was 400 mg/dL (range, 300–488 mg/dL) in the febrile neutropenia group compared to 820 mg/dL (range, 121–1700 mg/dL) in the control group (p = 0.003).The relative risk of developing chemotherapy associate febrile neutropenia in the presence of underlying hypogammaglobulinemia was 4.5 (95% confidence intervals, 1.9–10.7). Conclusions: Patients with CLL who are hypogammaglobulinemic are candidates for prophylactic administration of intravenous immune-globulin prior to initiation of myelosuppressive chemotherapy. [Table: see text] No significant financial relationships to disclose.
Phase I trial of pemetrexed (P) in combination with cetuximab (C) and concurrent radiotherapy (RT) in patients (pts) with head and neck cancer (HNC)
Authors: R. Smith, M. V. Karamouzis, D. E. Heron, R. L. Ferris, S. Y. Lai, S. Kim, T. Boyer, J. R. Grandis, J. T. Johnson, A. Argiris
Journal: Journal of Clinical Oncology (2007)

16516 Background: P is a multitargeted antifolate that has demonstrated activity in HNC and radiosensitizing properties in animal models. C is a chimeric IgG1 monoclonal antibody directed against the epidermal growth factor receptor that has increased the survival of pts with stage III/IV HNC when added to RT. We conducted a phase I study to evaluate the dose-limiting toxicities (DLT) and maximum tolerated dose of P when combined with standard RT and C. Methods: Pts with high-risk HNC were enrolled and evaluated separately in 2 cohorts: pts with no prior head and neck RT (cohort A) and previously irradiated pts (cohort B). A loading dose of C 400 mg/m 2 was given intravenously 7 days prior to starting RT followed by 250 mg/m 2 weekly throughout RT. RT was given 2 Gy/day to a total dose of 70 Gy (cohort A) or 60–66 Gy (cohort B). P was administered intravenously on days 1 and 22 (and day 43 if &gt;60 Gy was delivered) according to the following design: Starting dose level (0)-350 mg/m 2 , dose level (-1)-200 mg/m 2 , dose level (+1)-500 mg/m 2 . Additional pts could be treated at a lower dose level while other pts were being evaluated at a higher dose level. Results: 18 pts have been enrolled (A: 14; B:4). 2 pts in cohort A were not evaluable and replaced (1 pt was noncompliant due to transportation issues and 1 pt had sudden death attributable to aspiration). Histological types: squamous cell (13), undifferentiated (1), medullary thyroid (1), adenoid cystic (1), and adenosquamous carcinomas (2). In cohort A, 2 DLT (both neutropenic fever with ANC &lt;500) occurred: 1/6 at dose level 0 and 1/6 at dose level -1. In cohort B, no DLT has occurred: 0/3 pts at dose level 0 and 0/1 pts at dose level +1. There were no grade (G) 4 non- hematologic toxicities. Other serious toxicities included: neutropenic fever (NF) with ANC &lt;1000 (n=1), G 3/4 neutropenia (n=3/n=4), G 3 dysphagia (n=5), G 3 dermatitis (n=3), G 3 mucositis (n=4), G 3 fatigue (n=1), and G 3 anemia (n=1). Due to the development of 3 cases of NF in cohort A the protocol was amended and prophylactic antibiotics were added. Conclusions: The addition of P to RT and C was feasible in pts with or without a history prior RT. Neutropenia and in-field toxicities were predominant but manageable. Pts are currently being treated at dose level +1 (P 500 mg/m 2 ). No significant financial relationships to disclose.
Prognostic significance of α1,6-fucosyltransferase (α1,6-FT) in non-small cell lung cancers (NSCLCs).
Authors: Rio Honma, Ichiro Kinoshita, Eiji Miyoshi, Utano Tomaru, Yoshihiro Matsuno, Yasushi Shimizu, Satoshi Takeuchi, Kichizo Kaga, Naoyuki Taniguchi, Hirotoshi Akita
Journal: Journal of Clinical Oncology (2013)

7550 Background: Lung cancer is one of the leading causes of cancer death throughout the world. A more sophisticated understanding of the pathogenesis and biology of NSCLCs could provide useful information for predicting clinical outcome and individualizing treatment. α1,6-FT is the only one enzyme responsible for the core α1,6-fucosylation of N-glycans of glycoproteins, including EGF receptor, TGF-β1 receptor, and integrin α3β1. Methods: α1,6-FT expression was studied by immunohistochemistry in a cohort of 129 surgically resected NSCLCs, classified categorically based on the proportion of positively stained cancer cells (high, &gt; 20%; or low, &lt; 20%), and analyzed statistically in relation to various characteristics, including histology, survival and prognosis. Results: High and low expression of α1,6-FT was found in 67 and 62 of 129 NSCLCs, respectively. Multivariate logistic regression analysis revealed a significant association between high α1,6-FT expression and non-squamous cell carcinoma (mostly adenocarcinoma), as compared with squamous cell carcinomas (odds ratio, 3.51; p = 0.008). Patients with tumors having high α1,6-FT expression had significantly shorter survival time than patients with tumors having low expression in potentially curatively resected NSCLCs (p = 0.03) and adenocarcinomas (p = 0.009), as well as in pStage I NSCLCs (p = 0.03) by the log-rank test. Surprisingly, in pStage I adenocarcinomas, 12 of 23 patients with tumors having high α1,6-FT expression died of lung cancer, although none of 15 patients with tumors having low expression died of lung cancer. High α1,6-FT expression was a significant and independent unfavorable prognostic factor in potentially curatively resected NSCLCs (hazard ratio, 1.81; p = 0.047) and adenocarcinomas (hazard ratio 2.39; p = 0.006) and in pStage I NSCLCs (hazard ratio 2.55; p = 0.03) by Cox’s proportional hazards model analysis. Conclusions: These results suggest that α1,6-FT may play a pivotal role for the biological characteristics of NSCLCs. α1,6-FT expression is associated with histology of NSCLCs, and may be a new prognostic marker for overall NSCLCs and adenocarcinomas.
Survival outcomes of plasma cell leukemia (PCL) in the United States: A SEER analysis.
Authors: Hari Prasad Ravipati, Jonathan L. Kaufman, Amelia A. Langston, Lawrence Boise, Christopher Flowers, Sagar Lonial, Ajay K. Nooka
Journal: Journal of Clinical Oncology (2013)

8609 Background: Plasma cell leukemia (PCL) is an aggressive plasma cell disorder that is associated with poor outcomes. Previous studies have shown improved survival with bortezomib-based regimens in this subset of patients undergoing stem cell transplant (SCT), but this may reflect referral bias. Current knowledge evaluating outcomes of PCL is limited in the era of novel agents. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) database from 18 registries for survival characteristics in PCL stratified by age, sex, race and the era of diagnosis. International Classification of Diseases for Oncology 3rd edition histology code 9733 was used to identify cases. Results: From 1973 to 2009, 74826 cases of myeloma and 479 cases of PCL were recorded. Survival data was available for 397 PCL patients. The median overall survival (OS) was 6 months (95% Confidence Interval (CI): 4.8 months – 7.2 months); and 1-year, 2-year, and 4-year OS rates were 34%, 20%, and 9% compared to corresponding myeloma survival rates of 66%, 52%, and 32%, respectively. Median overall survival differences were observed for women vs. men (7 months vs. 5 months, p=0.026); black vs. white patients (7 months vs. 5 months, p=0.01); and patients aged &lt;60 years vs. ≥ 60 years (9 months vs. 4 months; P=0.01), respectively. In addition, patients diagnosed after 2005 had superior median OS compared with patients diagnosed prior to 2005 (7 months vs. 3 months; P=0.005). Conclusions: Black patients, women and patients aged &lt;60 years have improved OS compared to white patients, males and patients aged ≥ 60 years. The survival benefit seen in patients diagnosed after 2005 may be attributed to the benefit conferred by access to new agents, but OS remains poor. Newer treatment approaches for managing PCL are clearly needed.
Whole genome sequencing of sporadic Burkitt lymphoma in HIV-infected and uninfected patients.
Authors: Deborah Ritter, Kimberly Walker, Myoung Kwon, Premal Lulla, Catherine M. Bollard, Andrea Sheehan, Helen E. Heslop, Richard A. Gibbs, David A. Wheeler, Martha P. Mims
Journal: Journal of Clinical Oncology (2013)

8577 Background: Burkitt Lymphoma is defined by canonical translocations between MYC and immunoglobulin IgH, IgK or IgL (8:14, 8:2, 8:22, respectively), and is commonly associated with HIV. The identification of HIV from sequenced samples is critical to understanding HIV-associated Burkitt Lymphoma. While recent novel gene mutations (ID3 and TCF3) have been implicated in functional roles, concomitant genomic structural variants and the interaction of HIV with structural variation is less well defined. Methods: We sequenced the whole genomes of 15 patients with 100bp paired-end reads on Illumina Hi-Seq platform, resulting in an average insert size of 278 (+/- 63) and coverage of 60X tumor and 30X normal. We included 7 HIV-negative, and 8 HIV-positive subjects. Sequencing reads were mapped to the reference genome using BWA. Large-scale structural variation was detected by the BreakDancer and Crest programs. Functional annotation was used to prioritize structural variants for validation. Single nucleotide variants and small insertions and deletions were detected by CARNAC, a somatic variation discovery pipeline. The subset of WGS reads that failed to align to the human reference genome were tested for the presence of HIV sequences by comparing the unmapped reads to a database of viral DNA sequences which included the common subtypes of HIV defined by Los Alamos. Reads matching HIV or EBV with an expectation value of &lt;10 -4 were analyzed to determine virus coverage and viral integration sites. Results: Canonical MYC-IgH translocations were identified in 9/15 (60%) tumor samples, with 2 additional subjects harboring either a deletion or an inversion near exon1 of MYC; 4 had no MYC rearrangement. MYC translocations occurred equally in both groups. TP53 and SMARC4 point mutations were observed recurrently in the HIV uninfected group but not in the HIV infected patients. Variable levels of HIV DNA sequence were observed in normal tissue of all HIV infected patients. Conclusions: Whole genome sequencing has identified known somatic variants in HIV infected and uninfected patients. Two genes, TP53 and SMARC4, appear to be differentially mutated, but additional samples are needed to achieve statistical significance.
Checkmate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.
Authors: Yelena Yuriy Janjigian, Antoine Adenis, Jean-Sebastien Aucoin, Carlo Barone, Narikazu Boku, Ian Chau, James M. Cleary, Kynan Feeney, Fabio Andre Franke, Markus Moehler, Enrique Luis Roca, Michael Schenker, Mingshun Li, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2017)

TPS213 Background: The combination ofoxaliplatin and fluoropyrimidine is a standard-of-care (SOC) first-line treatment of pts with metastatic G/GEJ cancer, resulting in a median overall survival (OS) of 8–11 months and objective response rate (ORR) of 30%–50%. This is accompanied by up to 77% grade 3/4 toxicities. Therefore, new treatment options are needed to improve survival and decrease toxicity in G/GEJ cancer. Nivo, a fully human IgG4 monoclonal antibody (mAb) that targets programmed death 1 (PD-1) and ipi, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte–associated protein 4, have demonstrated manageable safety profiles and efficacy in multiple tumor types and may have a synergistic effect. In a phase 1/2 study in chemotherapy-refractory pts with G/GEJ/esophageal cancer with or without PD-1 ligand 1 (PD-L1) expression, second-line nivo 1 mg/kg + ipi 3 mg/kg demonstrated a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), median OS of 6.9 months, and a 34% OS rate at 12 months (Janjigian Y, et al. J Clin Oncol. 2016;34[suppl][abstract 4010]). This open-label, phase 3 trial will evaluate nivo + ipi as first-line therapy for pts with G/GEJ cancer (CheckMate 649; NCT02872116). Methods: In this study, 870 pts aged ≥ 18 years with untreated advanced or metastatic G/GEJ cancer with or without PD-L1 expression will be randomized to receive nivo + ipi (4 doses; followed by nivo monotherapy) or investigator’s choice of capecitabine/oxaliplatin (XELOX) or fluorouracil/leucovorin/oxaliplatin (FOLFOX). Tumor tissue for determination of PD-L1 status must be provided from ≤ 6 months before study treatment. Pts receiving chemotherapy or radiotherapy for G/GEJ cancer within the last 6 months or pts with suspected autoimmune disease, uncontrolled medical disorder, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ tumors. Secondary endpoints include OS in all pts and progression-free survival and time to symptom deterioration in all pts and pts with PD-L1+ tumors. Clinical trial information: NCT02872116.
Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): Final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG)
Authors: V. Diehl, H. Haverkamp, R. Mueller, H. Mueller-Hermelink, T. Cerny, J. Markova, A. D. Ho, L. Kanz, R. Greil, A. Engert
Journal: Journal of Clinical Oncology (2009)

8544 Background: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients. The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2x2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded for various reasons resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most prominent differences between pooled chemotherapy arms were anemia (65% 8BE vs 51% 4BE+4BB) and thrombopenia (65% vs 51%). Treatment outcome: complete remission 92.4%; early progression 2.2%; progression/relapse 7.8% (6.6% and 8.5%). A total of 156 (9.9%) deaths (72 vs 84) have been observed (22 vs 32 acute or salvage treatment toxicity; 15 vs 24 HL; 22 vs 13 secondary neoplasia). Most treatment related deaths occurred in the &gt;60 years age group, the first 4 cycles and the IPS&gt; 3 RF groups. Secondary neoplasias were observed in 77 patients (4.9%). At 5 years, OS was 91%, FFTF 85.5% and progression free survival (PFS) 86.2% (Kaplan-Meier estimates). Estimates for the difference at 5 years are 1.8% for OS, 2.3% for FFTF and 2.7% for PFS favoring BE. However, there was no statistical difference between 8x BE and 4BE+4BB in all outcome parameters (p&gt;0.19, log rank test). There is also no significant difference between the RT or no-RT arms in this study. Conclusions: The adoption of 4BE+4BB as a new standard in the future GHSG studies will depend on a refined analysis of the total data set and will be presented. No significant financial relationships to disclose.
Delivery of adjuvant chemotherapy (AC) to veterans with resected colon cancer.
Authors: Heather Dawn Riggs, Kathleen A. Lane, Patrick J. Loehrer, Siu Hui, Susan Rawl, Anne Ormerod, Michael Weiner
Journal: Journal of Clinical Oncology (2012)

e16557 Background: Patients (pts) with incomplete administration of AC for colon cancer (CC) likely experience inferior survival while oxaliplatin- and capecitabine-containing AC may not improve survival for older pts. The influence on AC completion of age, other baseline patient characteristics, or regimen characteristics is unknown. We evaluated the association of baseline characteristics and planned AC regimen with AC delivery in resected CC pts. Methods: This retrospective cohort study identified stage II and III resected CC pts from our local VA Medical Center tumor registry who initiated AC between 2004 and 2010. AC delivery was measured as percentage of planned cumulative dose (PCD) of 5-fluorouracil or capecitabine delivered. Baseline characteristics were demographics, CC stage, travel distance to the treatment site (TD), Adult Comorbidity Evaluation-27 score, and labs. We classified AC as fluoropyrimidine (oral or IV)-based and as oxaliplatin-containing. Linear regression tested each association with PCD. We recorded occurrence of toxicity and death. Cox regression models were used for survival analysis. Results: Fifty pts (98% male, median age 63) initiated AC for stage II (n=6) or III (n=44) disease with median interval from resection to AC of 7.4 weeks. The median PCD was 75%; median treatment duration was 5 months. Lower PCD was associated with older age (p=0.05), lower GFR (p=0.05), higher TD (p=0.02), lower baseline hemoglobin (p=0.10), and receipt of capecitabine (p&lt;0.01). Receipt of capecitabine (p=0.008) and TD (p=0.04) remained significantly associated with PCD in a multiple linear regression model. Toxicity was noted for 78%, and PCD tended to be lower for reported cardiac events (p=0.07). Pts older than 63 had inferior survival (HR=4.17, p=0.03). Pts receiving less than 80% PCD tended toward inferior survival (HR=4.31, p=0.07). Conclusions: Capecitabine-based AC and travel distance were associated with lower PCD, which may negatively impact survival. Efficacy of shorter courses of oxaliplatin-based chemotherapy is being evaluated elsewhere. Close attention to quality prescribing and monitoring practices for capecitabine are recommended. These findings should be confirmed in a larger cohort.
Understanding causes of distress in women with gynecologic malignancies.
Authors: Kerri S. Bevis, Guilherme Henrique Cantuaria, Rodney Paul Rocconi, Michael Finan, Jennifer Scalici, Gabrielle Betty Rocque, Elizabeth Ann Kvale, Aras Acemgil, Richard A. Taylor, Wendy Demark-Wahnefried, Kelly Kenzik, Karen Meneses, Michelle Martin, Mona Fouad, Edward E. Partridge, Maria Pisu
Journal: Journal of Clinical Oncology (2015)

e20686 Background: Lay patient navigators can screen patients using a distress tool (DT) to identify and address multiple patient concerns. Patient-reported distress can be used to characterize the needs of patients with ovarian, endometrial, and cervical cancer through all phases of care from initial diagnosis through active treatment and into survivorship. Methods: The Patient Care Connect Program (PCCP) includes 12 cancer centers throughout Alabama, Mississippi, Georgia, Florida, and Tennessee and navigates Medicare beneficiaries with cancer. Within the PCCP, navigators documented distress levels, causes of distress, and requests for intervention. Distress screening results were used to describe needs of patients with gynecologic malignancies and to assess effective resolution of distress. Results: Initial DT results were collected on 360 patients with gynecologic cancers: 206 (57%) ovarian, 111 (31%) endometrial, and 43 (12%) cervical cancers. Fifty-six (16%) were African American. Twenty-four percent of patients reported a distress score ≥ 4 and 4% reported scores ≥ 8. Physical symptoms most frequently caused distress (44%) particularly fatigue, pain, and neuropathy. Practical problems (11%), informational needs (16%) and emotional issues (19%) were also common. Patients were most likely to request assistance with transportation (63%), financial/insurance issues (77%), and nutritional concerns (75%). Lay navigators were able to address these concerns in 92% of patients. Conclusions: Gynecologic cancer patients report diverse sources of distress extending beyond symptom management. By administering DTs, patient navigators may effectively facilitate resolution of patient identified distress. The project described was supported by Grant Number 1C1CMS331023 from the Department of Health and Human Services, Centers for Medicare & Medicaid Services. The contents of this abstract are solely the responsibility of the authors and do not necessarily represent the official views of the U.S. Department of Health and Human Services or any of its agencies.