tbuckley/cabot-search huggingface dataset:
Effect of chemoradiation-related lymphopenia on survival in patients with unresectable, locally advanced pancreatic adenocarcinoma.
Authors: Aaron Tyler Wild, Ani Sarkis Balmanoukian, Dan Laheru, Lei Zheng, Phuoc T. Tran, Amy Hacker-Prietz, Susannah G. Yovino, Rachit Kumar, Mark A. Ziegler, Timothy M. Pawlik, Christopher Lee Wolfgang, Stuart A. Grossman, Joseph M. Herman
Journal: Journal of Clinical Oncology (2012)

307 Background: Pancreatic ductal adenocarcinoma (PDA) has been shown to elicit antitumor cell-mediated immune responses. In high grade gliomas, treatment-related lymphopenia has been associated with shorter survival. This study was performed to determine if patients with locally advanced PDA treated with definitive chemoradiation therapy (CRT) develop significant lymphopenia and if this affects overall survival (OS). Methods: A retrospective analysis of patients with locally advanced PDA treated at a single institution with CRT from 1997-2009 was performed. Serial lymphocyte counts were recorded and OS was analyzed as a function of lymphopenia and known prognostic factors. Results: 99 patients met eligibility criteria (≥18 years of age, ECOG performance status 0-2, and had baseline/follow-up lab values measured at our institution). Mean age was 61.6 years (SD, 11.6), 55% were male, mean tumor size 4.1 cm (SD, 1.6), and 97 had stage III disease. Median pre/post-CRT CA19-9 values were 241.5 and 105.2 U/mL, respectively. Total lymphocyte counts were normal in 87% of patients prior to RT. Mean RT dose was 47.3 Gy (SD, 8.2) and concurrent chemotherapy was 5-FU (67%), gemcitabine (20%), taxotere (7%), or none (6%). Chemotherapy dose reduction was necessary in 9%, and 39% required a RT break. Total lymphocyte counts fell to ≤500 cells/mm 3 in 51% two months after initiating CRT with a median reduction of 66% from baseline (p&lt;0.0001). Median OS of patients with lymphocyte counts ≤500 cells/mm 3 at 2 months was 7.7 months (95% CI, 6.8-8.7) versus 15.4 (95% CI, 11.9-19.0) for patients with &gt;500 cells/mm 3 (p&lt;0.001). Univariate analysis additionally revealed that among pre-treatment patient characteristics, only age ≥65 was significantly associated with OS (8.8 vs. 11.4 months; p=0.043). Type of concurrent chemotherapy was not significantly associated with OS. Multivariate analysis revealed a significant association between survival and lymphocyte count (&lt;500 vs. ≥500 cells/mm 3 ) at 2 months post-CRT (HR 3.8, p&lt;0.001). Conclusions: Definitive CRT induced lymphopenia is frequent, severe, and appears to be an independent predictor for OS in patients with locally advanced PDA.
A novel antibody that can detect a serum biomarker: Utility for detection and prognosis in colorectal and pancreatic cancer.
Authors: J. A. Bristol, J. Luka, M. Semenuk, I. H. Sbeitan, M. Thomas, P. M. Arlen
Journal: Journal of Clinical Oncology (2011)

e21121 Background: The early diagnosis of colorectal and pancreatic cancers remains an area of high unmet medical need. These cancers are currently diagnosed with non-laboratory procedures that are often invasive and expensive. As an alternative diagnostic approach, we developed two ELISA tests based upon two unique and promising novel tumor-specific monoclonal antibodies that we generated against a clinically tested human colon cancer vaccine. The NEO-151 and NEO-251 reagent antibodies bind to protein antigen biomarkers expressed by human tumors, with particular selectivity for colorectal and pancreatic tissues. In immunohistochemical testing, NEO-151 and NEO-251 did not react significantly with tissues from healthy donors. Methods: Sandwich ELISAs were developed with the NEO-151 and NEO-251 antibody as the capture reagent. The assays were used to evaluate colorectal and pancreatic cancer patient serum (n=102), serum from healthy blood donors (n=28), and serum from potentially interfering disease states (n=56) such as irritable bowel syndrome, Crohns disease, asthma, and chronic obstructive pulmonary disease. Results: Preliminary results showed that the serum from colorectal and pancreatic cancer patients, compared with serum from healthy controls, demonstrated each assay’s ability to differentiate the two groups with an average of 87% sensitivity and 87% specificity. Moreover, the ELISA results were reproducible among repeat tests, different operators, and were not influenced by testing serum from potentially interfering disease states. Conclusions: The proof of concept has been established for the potential value of the NEO-151 and NEO-251 antigen detection assays, suggesting a new cost effective scalable serum biomarker ELISA for potentially diagnosing and monitoring treatment of colorectal and pancreatic cancers. Of particular merit was the lack of significant interference by serum from potentially problematic disease states. These results support further development and large-scale early non-invasive diagnostic screening of normal populations for colorectal and pancreatic cancer, as well as analysis by multivariate analyte testing.
Predictors and prognostic implication of pathologic fracture (PF), spinal cord compression (SCC), and bone surgery (BS) following diagnosis of metastatic prostate cancer (PCa).
Authors: Ebere Onukwugha, Candice Yong, C. Daniel Mullins, Brian S. Seal, Arif Hussain
Journal: Journal of Clinical Oncology (2013)

133 Background: Information is limited about the predictors of PF, SCC, or BS and their relationship with PCa mortality in older men diagnosed with metastatic PCa. Methods: We analyzed patients aged 66 or older from the linked Surveillance, Epidemiology, and End Results &amp; Medicare (SEER-Medicare) database. Cases were diagnosed with M1 PCa between 2000 and 2007. Patients surviving at least 30 days post-diagnosis were identified and followed until death or censoring in December, 2009. Post-diagnosis occurrence of PF, SCC, and BS was identified using Medicare claims. (Multinomial) logistic and Cox proportional hazards regression models controlled for demographic characteristics, preventive service use, comorbidity status, and performance status proxies. Survival models were estimated in the full sample (FS) and in a propensity-score matched sample (PSMS). The survival requirement was relaxed and patients diagnosed with stage M1b were considered in sensitivity analyses. Results: Application of inclusion criteria resulted in 7,062 patients in FS (2,398 in PSMS). PCa-specific and all-cause mortality were 54% and 80% at a median (mean; min; max) follow up of 609 days (837; 30; 3,653). The average age for the sample was 78 yrs and 14% were non-Hispanic African American. The proportion with any event, SCC, PF, and BS were: 17%; 10%; 5%; 3%. Race, marital status, comorbid conditions, and health services use related to bone metastases were correlated with the likelihood of sustaining a PF, SCC, or BS, with differences based on the type of event. In the PCa mortality model the HR associated with each event was as follows using FS: [SCC] HR 1.12, 1.01 – 1.24; [PF] HR 1.14, 1.00 – 1.31; [BS] 0.61, 0.50 – 0.75. Results using PSMS were: [SCC] HR 1.04, 0.92 – 1.17; [PF] HR 1.11, 0.96 – 1.28; [BS] 0.58, 0.47 – 0.72. Relaxing the assumption of a minimum survival requirement did not change qualitative results. Conclusions: Patient demographics and clinical comorbid conditions correlate with the likelihood of sustaining PF, SCC or BS. Compared to fractures and spinal cord compression, the relationship between bone surgery and PCa-specific survival is more favorable.
Comparison of QOPI measure conformance between oncology fellows and attending physicians.
Authors: Tian Zhang, Arif Kamal, Michael J. Kelley
Journal: Journal of Clinical Oncology (2013)

162 Background: Quality improvement measures are uniformly applied to all oncology providers, regardless of their positions. Little is known about differences in conformance to these measures between oncology fellows and attending physicians. In order to tailor improvement interventions to these groups, we investigated conformance across QOPI measures for oncology fellows and attending physicians at the Durham VA Medical Center (DVAMC). Methods: Using data collected from the Spring 2013 QOPI cycle, we abstracted information from patients who had received care at the DVAMC between 2011 and 2013 and separated them based on their provider. To validate the data, we abstracted a subset of patient charts, limited to oral chemotherapy quality measures. Descriptive statistics and the Chi square test were calculated for each measure between the two groups. Results: A total of 97 patients were reviewed at DVAMC. Of these, 21 had a fellow and 47 had an attending as their main provider. Fellows and attendings performed similarly on 119 of 125 QOPI measures (core, end of life, symptom, colorectal, and NSCLC modules). Fellows were less likely to assess pain on the most recent visits when compared to attendings (52% vs. 77%, p=0.046) but more likely to document a management plan if the patient had moderate or severe pain (86% vs 75%, p=0.09). Attendings documented the plan for oral chemotherapy more often (93% vs. 60%, p=0.07). However, after the chart audit, we found that fellows actually documented the plan for oral chemotherapy 80% of the time (p=0.21). Fellows were more likely to document smoking status (95% vs. 64%, p=0.007) and to address smoking cessation (86% vs. 62%, p=0.048). Conclusions: Patient care practices tend to be similar between attendings and fellows overall; some of the significant differences may not remain significant after chart audit. Fellows generally mirror behaviors of attending physicians, and attendings have an important role in modeling best practice behaviors for fellows. Different quality measure standards may not be necessary between fellows and attendings.
Current landscape of acute myeloid leukemia quality measures in the United States.
Authors: Scott C Flanders, Cat N. Bui, Kyung Min Song, Eleanor Fitall, Kristi Mitchell, Stephanie Greenstein Braun, Erkut Bahceci, Bhavik Pandya, Dayo Jagun
Journal: Journal of Clinical Oncology (2016)

261 Background: Acute myeloid leukemia (AML) is a rare, but deadly hematological, disease with 20,830 new cases estimated in 2015 in the United States (US). As new treatments emerge, quality measures (QMs) will become important to assess the value of care. Our aim was to evaluate the current US AML QM landscape. Methods: We reviewed literature and online resources (eg, National Quality Measures Clearinghouse, Centers for Medicare &amp; Medicaid Services, etc.) published within the last 5 years to identify AML-specific and AML-related QMs. All QMs were categorized using a “continuum of care” framework according to the 5 stages of AML: 1) symptom assessment, 2) diagnosis/risk stratification, 3) initial treatment, 4) monitoring/additional treatment, and 5) advanced/late stage care. Quality measures were categorized by the measure type (eg, process or outcome measure) and use by the Centers for Medicare &amp; Medicaid Services (CMS). Results: In total, 30 QMs were identified: 1 leukemia-specific QM and 29 general oncology QMs. The leukemia-specific QM is a clinician-level process measure that evaluates the percentage of patients aged ≥ 18 years with a diagnosis of myelodysplastic syndrome or acute leukemia who had baseline bone marrow cytogenetic testing performed. Among the 29 general QMs: 8 are specific to stem cell transplantation, 13 are specific to chemotherapy, and 8 are general to oncology. Across the AML continuum of care: 2 QMs focus on symptom assessment, 1 supports diagnosis/risk stratification, 11 are for initial treatment, 9 for monitoring/additional treatment, and 7 for late-stage care. Twenty-seven QMs are based on process of care: 1 addresses resource utilization and 2 are outcomes based. The single leukemia-specific QM is used in CMS quality improvement programs, along with 3 other oncology-related QMs. Conclusions: While only one identified QM was specific to leukemia, other general oncology QMs may also apply. Unfortunately, QMs addressing AML-related morbidity and mortality are still lacking. Research into patient-centered communication, shared decision-making, patient-reported outcomes and resource use by AML patients may inform development of new QMs. Sponsorship: This research was funded by Astellas Pharma, Inc.
New molecular risk factors in germ cell tumors.
Authors: M. F. Sanmamed, E. Esteban, M. Capelan, A. Astudillo, G. Crespo, J. P. Berros, C. Muriel, P. Pardo, M. Izquierdo, E. Gutierrez, P. J. Fonseca, M. Luque, J. Fra, J. M. Vieitez, J. L. Perez-Gracia, S. Martin-Algarra, A. J. Lacave
Journal: Journal of Clinical Oncology (2011)

e21142 Background: Tumor histologic risk factors are inaccurate to predict risk of relapse in 25-30% of patients with clinical stage I germ cell tumors of the testis (CSIGCT), with important consequences in therapeutic strategies. The goal of this study is to identify new molecular criteria to improve the classic risk models of this cancer. Methods: From March 1976 to August 2010, sixty-nine patients with CSIGCT, independent of known risk factor or histology, were included in a surveillance program following orchidectomy. Paraffin-embedded GCT biopsies were reviewed for traditional histopathological features. Further, the samples were assessed for epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) and for mutations on exons 19, 20, and 21 by PCR. Univariate and multivariate analyses were performed to evaluate the role of these parameters as prognostic factors. Results: EGFR was expressed in 23.2% of tumors, but no EGFR mutations were detected in any of the exons studied. In the univariate analysis, EGFR expression showed significant relation with risk of relapse (p=0.04), while in the multivariate analysis, epididymis invasion was the only independent prognostic factor (p=0.02). In the subgroup nonseminoma germ cell tumors (NSGCT), the presence of embryonal carcinoma (EC) and vascular invasion (VI) were confirmed as prognostic factors. A risk model built on EC and VI yielded a 73.7% accuracy to predict relapse, whereas the addition of EGFR expression and epididymis invasion to the existing model increased accuracy to 91.6% in NSGCT. Conclusions: EGFR expression showed prognostic significance for prediction of relapse in CSIGCT. This additional molecular marker deserves further study to improve current models to manage this disease.
Patients as partners in managing cancer treatment-related toxicity.
Authors: Erin Redwood, Kathy Vu, Meaghan Wright, Colleen Fox, Noor Ahmad, Vicky Simanovski, Leonard Kaizer, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2016)

215 Background: Cancer Care Ontario is the government agency responsible for improving cancer services across Ontario’s 14 regions. To promote advances in best practices related to systemic treatment, Cancer Care Ontario hosts annual Systemic Treatment Safety Symposia, which serve as a platform to discuss quality and safety issues and results of quality improvement (QI) initiatives in alignment with the Systemic Treatment Provincial Plan. For the first time, the 2015 Symposium brought together patients and providers to discuss gaps and opportunities for improvement in relation to toxicity management (TM) during chemotherapy. The main goal of the event was to define improvement priorities. Methods: The Symposium presents a valuable engagement opportunity with regional stakeholders including medical oncologists, nurses, pharmacists, administrators and patient and family advisors. An interactive agenda was designed to elicit direction from these stakeholders. At the event attendees identified and prioritized improvement opportunities using a simulated investment scenario, where marked bills were given to participants to finance the solutions they felt would best address the challenges posed by current TM. The mock money was counted and analyzed based on the role of the ‘investors’ and the prioritized theme. Results: The Symposium had 92 attendees including 17 patients and caregivers. Themes that emerged are presented in the Table below. Endorsement varied depending on stakeholder group. For example, Access was the top improvement priority for patients, whereas Communication was highest for providers. Conclusions: A one day engagement event that brings together patients and providers can be successful in identifying priority areas for quality improvement. Based on the outcomes of the prioritization exercise, improving access to oncology providers for TM 24/7 was identified as a focus area for provincial and regional QI initiatives. [Table: see text]
An Analysis of Toxicities and Time to Engraftment Associated with Three Distinct Melphalan Treatment Schemas in Patients with Multiple Myeloma Receiving Autologous Hematopoetic Stem Cell Transplantation.
Authors: Ila Maewal, Andy J Kurtzweil, Jamie F Shapiro, Michael D Westmoreland, Roland L Bassett, Sergio Giralt
Journal: Blood (2008)
An open-label, single-group, phase 2 study of brentuximab vedotin as salvage therapy for males with relapsed germ-cell tumors (GCT): Results at the end of first stage (FM12GCT01).
Authors: Andrea Necchi, Domenico Magazzu, Andrea Anichini, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai, Maurizio Colecchia, Biagio Paolini, Elisa Coradeschi, Elena Tassi, Giulia Grazia, Roberta Mortarini, Giuseppina Calareso, Elena Togliardi, Flavio Crippa, Roberto Salvioni, Alessandro M. Gianni, Pinuccia Valagussa
Journal: Journal of Clinical Oncology (2016)

480 Background: Prognosis of patients (pts) failing multiple chemotherapy (CT) regimens is quite dismal. CD30 is expressed and prognostic in embryonal carcinoma, hence it is a rational target for treatment. Brentuximab Vedotin (BV) is an antibody-drug conjugate consisting of the chimeric anti-CD30 antibody SGN-30 conjugated to an antitubulin synthetic analog (MMAE). A phase 2 trial is ongoing in GCT (NCT01851200). Methods: 24 pts with biopsy-proven CD30+ GCT will receive BV 1.8 mg/Kg IV q3 weeks until disease progression or onset of unacceptable toxicity. Eligibility will include failure of 2 or 3 platinum-based CT (including HDCT). All pts will undergo measurement of serum tumor markers (STM), a computed tomography and a PET scan q6 weeks. An optimal Simon’s 2-stage design will be applied. The primary endpoint is the objective response-rate (ORR; H0: ≤ 5%, H1: ≥ 25%, α and β = 10%). In stage 1, 9 evaluable patients will be accrued. Sequential peripheral blood samples are being collected for immune profiling by flow cytometry of immune cell subsets. Results: From 07/13 to 04/15, 9 pts have been treated, 3 in third-line, and 6 beyond the third-line. 5 had received HDCT. STM decline was obtained in 7 pts (77.8%) after the first dose and in 4 pts (44.4%) after 2 doses (with normalized [1] or still positive [3] STM). ORR was 22.2% (1 CR+1 PR) according to RECIST v1.1, and there were 3 metabolic PR. 3-month PFS was 11.1% (95%CI: 0.6-38.8), 6-month OS was 85.7% (95%CI: 33.4-97.9). 1 case of reversible G3 hyperglycemia was recorded. No BV discontinuation due to toxicity occurred. In 7 evaluable pts, a trend to increasing expression of activation (HLA-DR), proliferation (Ki67), and functional differentiation (Granzyme B) markers in CD4 and CD8 T cells was observed during BV. In CR patient, an increased frequency of naive and central memory T cells was observed after the first cycle of BV, as well as a reduction in the fraction of PD1 + /CD8 + T cells. Conclusions: Brentuximab is endowed with potent antitumor activity and meaningful immunomodulatory effects in GCT. The rapid development of resistance is a concern. ORR is pending confirmation in the whole sample size. Clinical trial information: NCT01851200.
Targeting HER2/neu antigen to B cells via CD19 molecule: A vaccine approach for breast cancer immunotherapy.
Authors: D. Xiang, Y. Ma, C. Ding, G. H. Kloecker, J. Yan
Journal: Journal of Clinical Oncology (2011)

e13074 Background: Herceptin has been proven to be effective in the immunotherapy for Her-2/neu+ breast cancer. However, this adoptively transferred therapeutic Ab must be continuously given to the patient with huge financial cost. Thus, it would be desirable if tumor vaccines could elicit long-lasting Herceptin-like Ab. Methods: Constructing fusion protein of anti-mouse CD19 single chain variable fragment (anti-CD19-scFv) with human Her-2/neu extracellular domain P3-4 (P3-4) by extracting total RNA from Rat anti-mouse CD19 hybridoma (1D3) and first strand cDNA was synthesized accordingly. VH and VL were amplified using designed primers. Single chain Fv (VL-VH) was then synthesized by overlapping PCR. Then constructs were sequenced and cloned into pET-20b(+) vectors. Fragments P3-4 of extracellular domains of human Her-2/neu was cloned from pcDNA3.1-Her2 and then cloned into pET-20b(+)-scFv. Series of constructs were expressed and purified according to standard protocol and verified by Western Blot. Results: Both in vitro and in vivo studies demonstrated that fusion proteins anti-CD19-scFv and anti-CD19-scFv-P3-4 but not P3-4 could specifically bind to B cells with high affinity. Mice immunized with anti-CD19-scFv-P3-4 secreted higher titers of IgG and IgM than those from controls (p<0.05). Studies also demonstrated that sera from anti-CD19-scFv-P3-4 but not anti-CD19-scFv or P3-4 immunized mice stained with Her-2/neu expressing SKOV-3 tumor cells. These Abs also competitively inhibited Herceptin-mediated Ag binding, suggesting that Herceptin-like Ab responses were elicited. WT mice immunized with anti-CD19-scFv-P3-4 fusion protein then challenged with D2/F2-Her-2 mammary tumor cells showed significantly reduced tumor burden compared to those immunized with control fusion proteins (p<0.05) and had enhanced median overall survival to 45 days versus 34 days in WT mice immunized with either anti-CD19-scFv or P3-4. Conclusions: Targeting of Her-2/neu antigens to B cells stimulates Th-dependent humoral immune responses with anti tumor effect in mouse model. These findings provide a novel avenue for successful development of breast cancer vaccination strategy and help to fight for cancer.