tbuckley/cabot-search huggingface dataset:
Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients and modulation by GM-CSF-based anti-tumor vaccine
Authors: P. Filipazzi, R. Valenti, V. Huber, M. Iero, L. Pilla, G. Parmiani, M. Santinami, L. Rivoltini
Journal: Journal of Clinical Oncology (2007)

21082 Background: Phenotypic and functional features of myeloid suppressor cells (MSC), known to serve as critical regulators of anti-tumor T cell responses in tumor-bearing mice, are still poorly defined in human cancers. Here we analyzed myeloid subsets with suppressive activity present in peripheral blood of metastatic melanoma patients (MM) and evaluated their modulation by a GM-CSF-based anti- tumor vaccine. Methods: Stage IV AJCC MM patients (n=16) vaccinated with autologous tumor-derived heat-shock protein peptide complexes gp96 (HSPPC-96) and low dose GM-CSF provided pre- and post-treatment whole blood samples. Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry, separated into cellular subsets and used for in vitro proliferation assays. PBMC from stage- matched melanoma patients (n=12) treated with non-GM-CSF-based vaccines (i.e. HSPPC-96 alone or IFNa/melanoma-derived peptides) or gender and age-matched healthy donors (n=16) were also analyzed for comparison. Results: The lack or low levels of HLA-DR expression was found to identify a CD14 + cell subset with high suppressive activity on lymphocyte proliferation and functions. CD14 + HLA-DR -/lo cells were significantly expanded in all MM patients, while undetectable in healthy donors. Suppressive activity was mediated by TGFβ, as suggested by functional experiments with neutralizing specific antibodies. In contrast, no involvement of arginase and iNOS pathways could be detected. CD14 + HLA-DR -/lo cells, as well as spontaneous ex- vivo release and plasma levels of TGFβ, were augmented after administration of the HSPPC-96/GM-CSF vaccine. Interestingly, the expansion of suppressive CD14+ monocytes was associated to the inability to mount a significant CD8-mediated T cell response upon vaccination. On the other hand, no quantitative or qualitative enhancement of the CD14 + HLA-DR -/lo suppressive cell population was observed in patients receiving a non-GM-CSF based vaccine. Conclusions: CD14 + HLA-DR - /lo cells exerting TGFβ-mediated immune suppression may represent a new subset of myeloid suppressive cells, potentially expandable by the administration of GM-CSF-based vaccines in melanoma patients. [Table: see text]
Planning of internal mammary field based on lymphoscintigraphy localisation in post-operative radiation of breast cancer
Authors: M. S. Barsoum, M. M. Lotayef, A. M. Nasr, M. M. Kotb, A. Radwan, R. Mahmoud, O. Zaki
Journal: Journal of Clinical Oncology (2005)

909 The aim of this study is to determine the variability of position of the internal mammary (IM)lymph nodes using lymphoscintigraphy and to compare the dose of radiation that reaches these lymph nodes if only tangential fields are used together with its impact on the dose that reach the heart and lungs in different radiotherapy plans. Material and methods: this is a prospective study that included 30 breast cancer patients treated in the radiotherapy department of the NCI Cairo, indicated for p/o radiotion according to St. Gallen recommendations. Lymphoscintigraphy was done for all patients for detection of the exact site of the IM lymph nodes and a dose volume histogram (DVH) was done to measure the dose to the heart and lungs using CT planning. Two plans were done for each patient, the first with IM field, and the second without but with contralateral crossing of the mid line by 1 cm. Results: the mean percentage of the IM lymph nodes included in the IM field (plan I) was 70.03% # the second planning with only tangential fields (plan II) it was 3.05%. The radiation dose to the heart varies significantly (P: 0.001) in irradiation of the right side # the left side with a mean dose of 48.02% and 63.5%. The dose reaching the heart in plan I, ranged from 36.9% to 79.4% with the mean of 56.31% of total dose while in plan II it ranged from 2.3% to 16% with the mean of 8.51% of total dose with significant P value < 0.001. The dose reaching the lung in plan I ranged from 12.7% to 54.7% with the mean of 30.9% of total dose, while the dose in plan II ranged from 23.1% to 71.1% with the mean of 47.27% of total dose, with significant P value < 0.001. Conclusion: A direct IM field should be used if radiation is intended to this area. The planning of IM field should be adjusted according to lymphoscintigraphy so as to include all draining IM lymph nodes. In using IM field the risk of irradiation of a large volume of the heart increases, particularly in irradiation of the left side, while using tangential fields only will increase the late lung irradiation effects. In postoperative radiotherapy for breast patients, planning should be considered individually for each patient. No significant financial relationships to disclose.
The natural history of hepatic macroregenerative nodules developing in cirrhotic patients during surveillance with ultrasound.
Authors: M. Fraquelli, A. Sangiovanni, C. Della Corte, M. A. Manini, M. Iavarone, S. Vavassori, R. Romeo, A. Aghemo, L. V. Forzenigo, M. Colombo
Journal: Journal of Clinical Oncology (2010)

e14631 Background: Nonmalignant liver nodules (LN) are identified during the surveillance with abdominal ultrasound ( US) of cirrhotic patients for the diagnosis of early hepatocellular carcinoma (HCC). The natural history of LN is poorly understood. Aim: To prospectively evaluate the course of de novo nonmalignant LN detected during surveillance of cirrhotic patients. Methods: Consecutive Child Pugh A cirrhotic patients under surveillance with histologically proven de novo nonneoplastic LN were studied. Nonmalignant LN were followed with repeat US every 3 months and contrast enhanced CT/MR every 6 months. Fine needle biopsy (FNB) was repeated in nodules with increased size or a modified vascular pattern suggesting neoplastic transformation. Results: 31 nonmalignant liver nodules were detected in 30 patients, mean age 65 years (43-84), 51 (74%) males. Twenty-eight LN were between 1-2 cm in size including 25 macro-regenerative nodules (MRN) and 3 low-grade dysplastic nodules (LGDN). During a mean follow-up of 21 (7-34) months, 3 LGDN, all with arterial enhancement, progressed to HCC after 18 and 24 months, 8 MRN disappeared (3 with arterial enhancement, 1 with portal wash-out, 4 with neither vascular feature), and 20 remained unchanged (8 with arterial enhancement 4 with portal wash-out, 8 with neither feature). Additional LN developed in 10 patients including 1 HCC, 7 MNR, 2 undefined. Overall the mean yearly incidence of HCC was 6.2%. Liver cell dysplasia was the only significant predictive factor of HCC development (p = 0.002). Conclusions: Mean yearly incidence of HCC in nonneoplastic de novo LN detected in cirrhotic patients under surveillance is 6.2% with dysplasia being the only significant predictor of neoplastic transformation. No significant financial relationships to disclose.
Contrasting effects of religious/spiritual support from religious communities versus medical teams on advanced cancer patient end-of-life care.
Authors: T. A. Balboni, M. E. Paulk, M. J. Balboni, A. C. Phelps, T. Vanderweele, A. A. Wright, S. Block, H. G. Prigerson
Journal: Journal of Clinical Oncology (2010)

9012 Background: It is unclear how religious/spiritual (R/S) support from religious communities and medical teams compare in their relationship to advance cancer patients' medical care at the end of life (EoL). Methods: Coping with Cancer is an NCI/NIMH-funded, multi-site study of advanced cancer patients conducted from 9/2002-8/2008. Analyses were of 343 patients who were interviewed at baseline and followed until death a median of 117 days later. At baseline, patients rated support of their R/S needs by religious communities and by their medical team, with ratings dichotomized (a median split) to “largely” or “completely” supported versus supported “not at all,” “to a small extent,” or “to a moderate extent.” EoL care outcomes included (in the last week of life): hospice, number of aggressive EoL measures [care in an intensive care unit (ICU), resuscitation, and ventilation], and death in an ICU. Multivariable analyses simultaneously examined associations of religious community and medical team R/S support to the EoL care outcomes, controlling for confounding variables. Results: Patients reporting their R/S needs were largely or completely supported by their medical team were more likely to receive hospice care [OR = 2.99 (95% CI = 1.45-6.17), p = .003], received fewer aggressive EoL care measures [β = −0.19 (SE = 0.09), p = 0.04], and were less likely to die in an ICU [OR = 0.26 (95% CI = 0.07-0.92), p = 0.04]. In contrast, patients reporting their R/S needs were largely or completely supported by religious communities were less likely to receive hospice [OR = 0.38 (95% CI = 0.20-0.72), p = 0.003], received more aggressive EoL care measures [β = 0.21 (SE = 0.08), p = 0.01], and were more likely to die in an ICU [OR = 4.69 (95% CI = 1.51-14.56), p = 0.008]. Conclusions: In contrast to the association of R/S support from medical teams with less aggressive EoL care, R/S support from religious communities predicts greater aggressive care at the EoL. These findings suggest that EoL decision-making may be influenced by the content or source of R/S care provided to patients. Improved collaboration with and education of religious communities may be strategies to reduce aggressive care at the EoL. No significant financial relationships to disclose.
Further evaluation of <sup>11</sup>C-PD153035 as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in non-small cell lung cancer patients
Authors: J. Yu, N. Liu, M. Hu, X. Song, L. Xie, X. Meng, X. Wang, L. Kong, G. Yang
Journal: Journal of Clinical Oncology (2009)

3590 Background: Epidermal growth factor receptor (EGFR) plays a key role in tumorgenosis and is therefore an important target for new therapeutic and prognostic strategies. Our pilot study has demonstrated that 11 C-PD153035, a highly EGFR selective tracer for positron emission tomography (PET), accumulated in tumor mass of non-small cell lung cancer (NSCLC) and the tracer uptake correlated with EGFR expression. Here, we further evaluate correlation between the intensity of 11 C-PD153035 uptake and EGFR protein expression level and gene mutation. Methods: Fourteen patients (45–71y, mean 59.2±9.2 y, Male: Female = 8:6, squamous carcinoma: adenocarcinoma = 9:5) with pathologically proved NSCLC were examined with PET using 11 C-PD153035 one week before surgery. Radioactivity concentrations, derived from regions of interest (ROI), were analyzed mathematically to maximum standardized uptake value (SUVmax). The EGFR protein expression of surgical specimen was utilized by immunohistochemistry (IHC) with a three-tier system intensity scored and Western Blot assay. The EGFR genetic alterations in exon 19 and 21 were examined by direct sequencing of polymerase chain reaction (PCR) products. Results: 11 C-PD153035 uptake was observed in 9 out of 14 NSCLC patients (mean SUV 3.94±1.06, range 0.8–5.9) and the biodistribution study further demonstrated accumulation of radioactivity in the tumor mass. The SUVmax of 11 C-PD153035 molecular images did not correlate with tumor size and injection dose of the tracer. A closely correlation between SUVmax and EGFR protein expression as determined by IHC (r = 0.84, p = 0.005) was observed but not with the protein expression level of Western Blot analysis (r = 0.442, p = 0.114), as well as EGFR exon 19 (r = -0.078, p = 0.790) or exon 21 (r = 0.118, p = 0.689) gene mutation. With ROC analysis according to IHC intensity, the cut-off value of SUVmax was 2.45. Conclusions: PET with 11 C-PD153035 might therefore be used to visualize EGFR pattern on tumor in NSCLC patients and for individualized planning of therapeutic strategies with EGFR targeted drugs, especially small-molecule TKIs (gefitinib and erlotinib) which targeting the intracellular EGFR tyrosine kinase domain as PD153035. No significant financial relationships to disclose.
A provider-payor approach for determining value in the health reform era: Early reports on the mQure initiative.
Authors: Douglas D. Letson, Karen K. Fields, Diane K. Hammon, Rachel V. Lee, John W. Peabody, Alan F. List
Journal: Journal of Clinical Oncology (2013)

255 Background: Determining value requires detailed measurement of clinical services and associated costs. In the health reform era value demonstration presents a challenge for both providers and payors: providers, unable to demonstrate value, will be unable to attract payors or patients and expand market share; payors, unable to choose the right providers, will lose opportunities to lower costs and raise quality. Methods: In July 2012, the Moffitt Cancer Center (MCC) launched the mQure (MCC – Quality Understanding Research and Evidence) Initiative to (1) measure and improve clinical performance, (2) increase compliance to evidence-based/cost conscious cancer-care pathways, and (3) demonstrate value. We introduced Clinical Performance and Value (CPV) vignettes, a value measurement tool, to measure pathway adherence, determine diagnostic accuracy and appropriate use of diagnostic tools starting with breast and lung cancer. For selected performance items identified by the CPVs, we audited medical records directly. Results: Measurement revealed high value practices, for example, diagnostic accuracy, appropriate rates of biopsy and more accurate staging compared to other groups. Value determination led to one signed plus two pending payor partnerships to implement a shared savings contract, find ways to reduce utilization and explore creating payor-led networks. The focus on individual responsibility for adherence to evidence-based practices has had an unanticipated and seemingly paradoxical benefit of shifting the group to narrow practice variation thereby shifting providers to a more self-aware culture. An external benefit is that the value signal has led to discussions to form accountable care organization (ACO) networks for cancer care. Since mQure’s inception, MCC has created partnerships with 3 hospitals. Based on the breast cancer initiative alone, financial models indicate an estimated savings of up to $2 million annually that arise from higher quality, fewer unnecessary tests and improved pathway compliance. Conclusions: In just one year, the large scale mQure project has led to expanded provider partnerships, new quality-based arrangements with payors and the formation a specialty-ACO.
IND 205B: A phase II study of the PI3K inhibitor PX-866 and continued abiraterone/prednisone in patients with recurrent or metastatic castration resistant prostate cancer (CRPC) with PSA progression on abiraterone/prednisone.
Authors: Sebastien J. Hotte, Anthony M. Joshua, Vamsee Torri, Robyn Jane Macfarlane, Naveen S. Basappa, Jean Powers, Eric Winquist, Som Mukherjee, Richard William Gregg, Christian K. Kollmannsberger, Daygen L. Finch, Hao Xu, Diana Felice Hausman, Lesley Seymour, Elizabeth A. Eisenhauer, Kim N. Chi
Journal: Journal of Clinical Oncology (2015)

279 Background: PX-866 is an irreversible, pan-isoform inhibitor of Class I PI-3K. In part A of this study, PX-866 as a single agent was well tolerated and showed modest activity in CRPC but did not meet a priori benchmarks as a single agent in unselected patients (pts). As androgen receptor inhibition promotes PI3K activity in PTEN-loss PC models, the addition of PX-866 in patients whose PSA is rising on abiraterone acetate plus prednisone (AA+P) may reverse resistance and phase B of the study tested this hypothesis clinically. Methods: In this multicentre, phase II study, CRPC pts with PSA progression on AA+P received PX-866, 8mg daily on a 6-week cycle while continuing AA+P. Primary endpoint was lack of progression at 12 weeks (PCWG2 criteria). Secondary endpoints included PSA and objective response rates. PX-866 would be deemed worthy of further study if at least four of 25 pts were progression free at 12 weeks. Results: 25 pts were accrued and all are evaluable for toxicity and PSA response. Eleven pts had measurable disease of which 11 are evaluable for objective response. Median age was 72, ECOG PS was 0/1 in 10/15 pts. Eighteen pts received prior chemotherapy. Median number of cycles was 2 (range 1–3). 52% of pts received at least 90% of planned dose of PX-866. Most common adverse events (AEs) were fatigue (21 patients), diarrhea, (18), nausea (13), vomiting (11) and anorexia (12); one patient discontinued because of protocol therapy toxicity (grade 3 anemia). Other grade 3 AEs (one patient for each) were diarrhea, vomiting, fatigue, AST and ALT elevation and lymphocyte and platelet changes. Six pts were progression free at 12 weeks. No objective or PSA responses were seen. Of the pts with measurable disease, best objective response was stable disease in six (2.3-3.6m) and best PSA response was non-response in eight pts. Conclusions: The addition of PX-866 to AA+P in unselected pts progressing on AA+P shows no evidence of antitumour effects. Strategies to combine PI3K inhibition with AR targeted therapies should consider initiation earlier in the disease course and/or recruiting a selected population. Clinical trial information: NCT01331083.
Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen in the Breast International Group (BIG) 1–98 trial
Authors: K. E. Ribi, K. A. Phillips, Z. Sun, A. Stephens, A. Thompson, V. Harvey, B. Thürlimann, F. Cardoso, A. S. Coates, J. Bernhard
Journal: Journal of Clinical Oncology (2009)

510 Background: Hormonal therapy for breast cancer (BC) may affect cognition. Methods: Post-menopausal women with hormone receptor positive, early-stage BC were randomized to receive either: A) tamoxifen for 5 years; B) letrozole for 5 years; C) tamoxifen for 2 years followed by letrozole for 3 years; or D) letrozole for 2 years followed by tamoxifen for 3 years, as adjuvant endocrine treatment. During the fifth year of trial treatment, objective cognitive function (speed of psychomotor function, visual attention, working and verbal memory, learning) was evaluated by computerized tests. The difference in the composite score for patients taking letrozole (B+C; N= 65) versus tamoxifen (A+D; N = 55) at the time of testing was the primary comparison. Scores for each domain were standardized according to age-specific norms. Two-way ANOVA controlling for language was used to test the effect of treatment on cognitive function. Self-reported subjective cognitive function, psychological distress, fatigue and quality of life were also assessed. Results: Patient characteristics were balanced between groups. Both groups performed below age norms on most domains. The group taking letrozole had better overall cognitive function than the tamoxifen group (difference in mean composite scores = 0.278, p = 0.038, 95% CI: 0.015–0.540) and outperformed patients on tamoxifen for all domains (n.s.). Comparison of monotherapy arms A versus B supported better cognitive function among letrozole patients. Subjective cognitive function, psychological distress, fatigue, and quality of life did not differ between groups. Conclusions: Although letrozole results in lower circulating estrogen levels than tamoxifen, in this study BC patients taking adjuvant letrozole during the fifth year of treatment had better cognitive functioning than those taking tamoxifen. [Table: see text]
Bevacizumab in combination with radiotherapy plus concomitant and adjuvant temozolomide for newly diagnosed glioblastoma: Update progression-free survival, overall survival, and toxicity
Authors: M. L. Gruber, S. Raza, D. Gruber, A. Narayana
Journal: Journal of Clinical Oncology (2009)

2017 Background: Prognosis of glioblastoma (GBM) is very poor. Standard treatment includes surgical resection (SR), radiation (RT), concomitant and adjuvant chemotherapy with temozolomide (TMZ). Our objective is to assess the treatment efficacy, safety and survival in patients with newly-diagnosed GBM treated with RT, TMZ, and bevacizumab in the upfront management. Methods: From 2006–2008, 51 eligible patients (age &gt;18, KPS &gt;70) with newly-diagnosed GBM divided into two groups. Group A (n = 20) was treated with RT (60Gy) and concomitant TMZ (75mg/m 2 daily for 42 days) with bevacizumab (10mg/kg every 2 weeks), 29 days following surgery, followed by up to six cycles of adjuvant TMZ (150mg/m 2 ,daily x 7d, q28 with bevacizumab at 10mg/kg days 8 and 22 of each 28 day cycle. Group B (n = 31) received similar treatment without bevacizumab. Both groups were followed up until tumor progression (PFS). Recurrence was defined according to MacDonald Criteria. The end points were PFS, overall survival (OS) and toxicity. Results: Median bevacizumab infusions were 12 (4–32). Median follow-up was14 months for both groups. 6 months PFS survival in Group A was 77.5% and in Group B was 51.6%. Median PFS in Group A was 17 months compared to 7 months in Group B (p &lt; 0.0001, HR = 0.26). Median OS has not been reached in Group A and was 17 months in Group B. One and 2 year OS were 83% and 57% in Group A compared to 72% and 6.5% in Group B (p = 0.02) ). Post-RT and temodar toxicities include thrombocytopenia (1 patient; Gr 3 and fatigue (3 patient;1 Gr 3), bevacizumab related toxicities with RT include leg ulcer with cellulites (1 patient; Gr 3) and pulmonary embolism with thrombocytopenia (1 patient; Gr 4), hypertension (2 patients; Gr 1), and asymptomatic blood products on MRI (2 patients). Conclusions: Bevacizumab has demonstrated efficacy, acceptable toxicity, improved PFS and OS in the upfront management of GBM. No significant financial relationships to disclose.
GS-98-437 a double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) for the treatment of patients with HBeAg+ chronic hepatitis B infection: 48 week results.
Authors: Patrick Marcellin, Ting-Tsung Chang, Seng Gee Lim, Myron J Tong, William Sievert, Mitchell Shiffman, Lennox Jeffers, Zack Goodman, Jia Ma, Anant Jain, John Fry, Carol L Brosgart
Journal: Hepatology (2001)