tbuckley/cabot-search huggingface dataset:
Importance of Gleason score on <sup>18</sup>F-choline PET/CT findings in patients with biochemical relapse of prostate cancer disease (PSA&lt;1.0 ng/ml).
Authors: Marina Hodolic, Marino Cimitan, Jure Fettich
Journal: Journal of Clinical Oncology (2013)

86 Background: Not all tumors show significant increase of metabolic activity on 18 F-FDG PET/CT imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. As a component of cell membrane phospholipids, choline is an excellent biomarker for the malignant transformation and increased proliferation of cells. 18 F-choline ( 18 F-FCH) PET/CT is a nuclear medicine procedure that has greater sensitivity and accuracy than 18 F-FDG PET/CT to detect prostate malignancy: sensitivity 73% vs. 31% and accuracy 67% vs. 53%, respectively. The efficiency of FCH to detect prostate cancer disease before and after treatment is related to the PSA levels. Evaluation of recurrent disease with 18 F-FCH PET/CT imaging in patients with prostate cancer disease is becoming a routine procedure. Purpose: To investigate the role of Gleason score (GS), as a marker of proliferation, on 18 F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease defined as increased level of prostate specific antigen (PSA). Methods: 140 patients with biochemical relapse (PSA&lt;1.0 ng/ml) underwent 18 F-FCH PET/CT scan after treatment: radical prostatectomy, radiotherapy, hormonal therapy alone or combined treatment. Results: 18 F-FCH PET/CT detected prostate cancer recurrence in 97% of patients with GS&gt;7, 82% of patients with GS=7 and 63% of patients with GS&lt;7. All patients had PSA between 0.2 and 1.0 ng/ml. Out of 140 patients 43% had recurrence in prostatic bed and 57% patients had local metastasis. Conclusions: Prostate cancer proliferation defined as Gleason score, influence 18 F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease at any PSA level.
Bone health in postmenopausal women (PMW) with hormone-sensitive breast cancer (HSBC) receiving adjuvant aromatase inhibitor (AI) therapy
Authors: M. Kalder, P. Hadji
Journal: Journal of Clinical Oncology (2008)

11556 Background: AIs are approved for PMW with HSBC. The near complete reduction in estrogen synthesis with AIs exacerbates the risk for bone loss, osteoporosis, and bone fractures. Methods: Incidence of fracture and osteoporosis, bone mineral density (BMD), and bone turnover markers were evaluated in adjuvant AI trials (ATAC, BIG 1–98, ALIQUOT, IES, LEAP, MA.17). Results: In healthy PMW, all AIs (steroidal or nonsteroidal) are associated with increased bone turnover markers. In PMW with HSBC, any AI (anastrozole [ANA], exemestane [EXE], or letrozole [LET]) decreases BMD and increases fracture and osteoporosis rate vs either placebo (PLA) or tamoxifen (TAM) regardless of treatment setting (Table). After 5 years of ANA, PMW shifted from normal to osteopenic BMD and lost about 8% BMD at the spine and hip. In IES, increased bone turnover was seen in PMW who switched to EXE following prior TAM. Similar findings were seen in PMW who had prior TAM in ALIQUOT. AI-associated bone loss stabilizes with completion of therapy and is attenuated when zoledronic acid (ZOL) is added to the treatment regimen in either pre- or PMW. Conclusions: Irrespective of setting and class, all AIs decrease BMD and increase bone turnover markers, resulting in increased risk for osteoporosis and bone fractures. Concomitant use of ZOL can attenuate these risks. Current guidelines rely solely on the presence of osteoporosis (BMD < -2.5) to guide bisphosphonate intervention. As 80% of fractures occur in osteopenic women, this threshold appears inadequate for averting fractures in PMW with HSBC. It would be prudent to give ZOL 4 mg twice yearly to PMW who are taking AIs and have a T-score < -2.0, and those with any 2 following risk factors: T-score < - 1.5, age >65 years, family history of hip fracture, personal history of fragility fracture after age 50, smoking, or oral corticosteroid use >6 months. Setting Trial N FU (mo) Lumbar BMD (%) Fracture rate (%) Ref Upfront ATAC bone substudy 167 60 − 6.1 ANA +2.8 TAM Coleman 2006 ASCO abs 511 ATAC 6241 68 11.0 ANA* 7.7 TAM Howell 2005 Lancet BIG 1–98 8010 25.6 NR NR 5.7 LET* 4.0 TAM Thürlimann 2005 NEJM Switch IES bone substudy 206 24 −4.0* EXE −0.6 TAM Coleman 2007 Lancet Oncol IES 4724 58 7.0 EXE* 5.0 TAM Coleman 2007 Lancet Oncol Extended MA.17B 226 24 −5.4 LET* −0.7 PLA Perez 2006 JCO MA.17 5187 30 5.3 LET 4.6 PLA Goss 2005 JNCI *P<0.01; NR=not reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Elly Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, Roche, Schering, Solvay, Wyeth
The prognostic influence and interrelationships of CD8<sup>+</sup> T-cell infiltration in malignant colorectal tumors.
Authors: C. H. Richards, A. Powell, S. Platt, C. S. Roxburgh, D. C. Mcmillan, P. G. Horgan
Journal: Journal of Clinical Oncology (2011)

3596 Background: The mechanisms explaining the impact of immunosurveillance on tumour development are unclear. The aims of the study were to (1) examine the prognostic influence of CD8+ T cell infiltration in malignant colorectal tumours and (2) investigate relationships with clinical and pathological variables. Methods: Patients undergoing resection of colorectal cancer (1997 – 2007) were identified from a prospective database. Clinical variables included systemic inflammatory response as defined by the modified Glasgow Prognostic Score (mGPS). Pathological variables included H&E assessment of the inflammatory cell infiltrate as defined by the Klintrup-Makinen criteria (KMC). Tumour blocks were retrieved and new sections stained for CD8+ T cells. CD8 infiltration was assessed by two independent observers in 3 tumour areas; the invasive margin (IM), tumour stroma (ST) and cancer cell nests (CCN). Results: 324 patients (146 females, 178 males) who underwent resection of stage I (8%), stage II (49%) or stage III (43%) colorectal cancer were included. mGPS assessed the systemic inflammatory response as ‘0’ (55%), ‘1’ (31%) or ‘2’ (14%). KMC graded the inflammatory cell infiltrate as weak (65%) or strong (35%). CD8 infiltration was graded as absent, weak, moderate, strong; CD8-IM 19%, 41%, 30%, 10%; CD8-ST 26%, 47%, 20%, 7%; CD8-CCN 32%, 37%, 19%, 12%. On multivariate analysis, age (HR 1.67, p=0.002), TNM stage (HR 1.90, p=0.009), vascular invasion (HR 1.99, p=0.003), mGPS (HR 1.98, p<0.001), KMC grade (HR 2.33, p=0.027) and CD8-CCN (HR 1.44, p=0.012) were independent predictors of cancer specific survival. There were close relationship between CD8-CCN, CD8-IM and KMC grade (p<0.001). CD8-CCN was strongly associated with an absence of vascular (p<0.01) or perineural (p<0.01) invasion. Conclusions: CD8+ T cells are an important component of the local inflammatory cell infiltrate seen in the microenvironment of malignant colorectal tumours. Abundant CD8-CCN in particular is an independent prognostic indicator and may confer a survival advantage through the prevention of vascular and perineural invasion.
Prognostic value of gender in hospitalized pancreatic patients.
Authors: Shuang Yin Zhang, Shuang Qin Zhang, Jimmy Jing Jiang, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2015)

256 Background: Women with pancreatic cancer (PC) are known to have a longer overall survival compared with men. However, no data address the association of gender with acute medical complications in the inpatient setting. We hypothesize that women with PC have fewer inpatient medical complications than men. Methods: The Nationwide Inpatient Sample (NIS) database was queried to identify all non-surgical hospital admissions for patients with a diagnosis of pancreatic cancer for 2011. We compared inpatient complications and mortality between females and males with PC using univariate and multivariate logistic regression model. Two sample independent t-tests were used to compare all linear variables, and Chi-squared tests were used to compare categorical data. Results: Of the 16,616 PC patients analyzed, there were 8,324 females (F) and 8,292 males (M). Mean age was 69 (F) and 67 (M). Length of stay for both averaged 6 days. After adjusting for gender, age, race, inpatient chemotherapy, and comorbidities (depression, alcoholism, arthritis, coagulopathies, drug use, diabetes, hypertension, hypothyroidism, liver disease [dz], metastatic dz, obesity, perivascular dz, renal failure), multivariate analysis showed that male gender in PC patients is independently associated with increased incidence of pneumonia (p&lt;0.001, RR 0.77), pulmonary embolism (p=0.006, RR 0.80), ileus (p=0.001, RR 0.79), and acute renal failure (p&lt;0.001, RR 0.76). Female patients experienced higher incidence of urinary tract infection (p&lt;0.001, RR 1.9). Although incidence of mortality for male patients with PC was higher by univariate analysis (p= 0.005), it was not significantly higher by multivariate analysis (p= 0.087). Conclusions: In this study, men admitted with PC suffer higher incidences of inpatient complications compared to women. These findings may partly explain the higher overall survival rate of women compared to men with PC. It also implicates gender as prognostic tool in the management of hospitalized PC patients.
Circulating mediators of inflammation in AIDS-related non-Hodgkin lymphoma.
Authors: Brian Michael Nolen, Frank J. Jenkins, Lawrence Kingsley, Lisa P. Jacobson, Charles R. Rinaldo, Anna Lokshin
Journal: Journal of Clinical Oncology (2012)

86 Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries, accounting for 3-6% of AIDS-defining illnesses and 23-30% of AIDS-related mortality. The risk of developing NHL is estimated to be 60 times greater in HIV-infected individuals in comparison to the general population and this rate has remained elevated despite the advent of HAART. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male patients diagnosed with high-grade B-cell NHL. Controls were matched to each case from among those participants who developed an AIDS-defining opportunistic infection in the absence of any malignancy. Matching criteria included age and CD4+ cell count. Sera obtained from each patient near the time of NHL or AIDS diagnosis was tested for a panel of 171 serum biomarkers using multiplexed bead-based immunoassays. Biomarker measurements were evaluated to identify significant alterations between the experimental groups, correlations with disease progression and interactions between biomarkers. Results: A subset of 21 biomarkers was identified to be significantly altered in A-NHL cases in comparison to the AIDS controls. This subset included cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators. Many of the biomarkers included in this subset were positively correlated with disease progression. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in response to persistent immune stimulation and inflammation. A network of inflammatory mediators was identified demonstrating correlations with disease progression and overexpression in A-NHL patients. Further analysis of these biomarkers should enhance our ability to diagnose, monitor, and treat this disease.
Mutation frequency in <i>BRAF</i> and <i>NRAS</i> genes among primary tumors and different types of metastasis from melanoma patients.
Authors: M. Colombino, M. Capone, M. Maio, V. De Giorgi, A. Cossu, A. Lissia, C. Rubino, B. Massidda, S. Staibano, O. Nappi, G. Botti, C. Caraco, N. Mozzillo, A. Manca, M. Sini, P. A. Ascierto, G. Palmieri
Journal: Journal of Clinical Oncology (2011)

8574 Background: Mutations of NRAS and BRAF genes have been identified with high frequency in nevi, cutaneous melanomas, and melanoma metastases. Prevalence of such mutations during the disease progression phases and among the different types of metastasis still remains inconclusive. Methods: Paired samples of microdissected invasive primary melanomas (N=73) and synchronous or asynchronous metastases (N=164) from same patients underwent mutation analysis by automated DNA sequencing. Secondary lesions were from: regional (RN; N=49) or distant (DN; N=16) lymph nodes; regional (RS; N=16) or distant (DS; N=18) skin; visceral (VM; N=22) and brain (BM; N= 44) sites. Results: To date, mutations were identified in 44/73 (60%) primary melanomas [42% BRAF - 18% NRAS], 43/65 (66%) lymph nodes [49% BRAF - 17% NRAS], 21/34 (62%) subcutaneous metastases [38% BRAF - 24% NRAS], 13/22 (59%) visceral metastases [45% BRAF - 14% NRAS], and 31/44 (70%) brain metastases [48% BRAF - 23% NRAS]. Overall, a slight and not significant increase in mutation frequency after progression from primary melanoma was observed in our series: 108/164 (66%) mutated metastases [46% BRAF - 20% NRAS]. The only significant differences were found for subcutaneous metastases: a) DS presented a significantly higher mutation frequency than RS (78% vs. 44%); and b) a discontinuous pattern of BRAF/NRAS mutations was detected in primary melanomas vs. RS and DS lesions. These latter findings suggest that independent subclones may have been generated. Conclusions: Although collection and analysis of samples is still ongoing, our results may provide further clues about the impact of NRAS and BRAF mutations among the different stages of melanoma progression.
Ewing sarcoma prognostic score (ESPS) at diagnosis, based on fever and metastatic status.
Authors: N. Gaspar, G. Le Teuff, A. S. Defachelles, C. Schmitt, D. Levy, M. P. Castex, O. Lejars, C. Verite, E. Plouvier, L. Claude, O. Oberlin
Journal: Journal of Clinical Oncology (2011)

9539 Background: Our purpose was to identify prognostic factors in Ewing's sarcoma (ES) at diagnosis that could allow better treatment stratification. Methods: Between 1988 and 1999, 486 patients (pts) with localized (n=364) or metastatic (n=122) ES were enrolled in two French protocols EW88 and EW93. Characteristics at diagnosis of the patient (age, gender, fever) and of the tumor (initial tumor volume (ITV), primary location, presence and type of metastasis [METS]) were prospectively collected and their influence on disease-free survival (DFS) was assessed. Results: With a 8.5 years median FU, the number of events is 242 (49.8%). By univariate analysis, the following features were found to be associated with a poor prognosis: age <7 or ≥15 years (p=0.001), axial and proximal (femur, humerus) location (p=0.0001), presence of fever (p<.0001), ITV > 200 ml (p<.0001), metastases (p<.0001). In metastatic patients, prognosis for lung only mets was better than for other mets (p=0.006). In the multivariable analysis, the presence of fever and the metastatic status remained prognostic and serve to build a prognostic score summing these two variables assigning a two score point for “other mets” (cf table). This resulted in four groups with significant different 5-year DFS: 60% for ESPS=0 (localized tumour without fever), 47% for ESPS=1 (localized tumor with fever or isolated lung mets without fever, HR=1.47), 29% for ESPS=2 (isolated pulmonary metastasis with fever or other metastasis without fever, HR=1.75) and 10% for ESPS=3 (febrile patients with other mets, HR=5.12). Conclusions: The Ewing Sarcoma Prognostic Score identifies, at diagnosis, very different prognostic groups which might benefit from different treatment strategies. The prognostic value of this ESPS warrants confirmation in a large independent population. Fever Isolated lung mets Other mets No. (%) of patients 5-year DFS Prognostic score ESPS 5-year DFS byscore Hazard ratio [95%CI] P value 0 0 0 302 (65) 60% 0 60% 1 1 0 0 49 (10) 46% 1 47% 1.47 [1.06-2.06] 0.023 0 1 0 43 (9) 47% 1 1 0 11 (2) 27% 2 29% 1.75 [1.16-2.64] 0.007 0 0 2 40 (9) 29% 1 0 2 22 (5) 10% 3 10% 5.12 [3.00-8.73] <0.001
New tools for enhancing the quality of phase I clinical trials: The Armada and Labtracker computer systems.
Authors: Daniel D. Karp, Gerald Steven Falchook, Harihara Subramanian, Passion Lockett, Dina Harleaux, Cheryl Fullmer, Badi Edmond El Osta
Journal: Journal of Clinical Oncology (2013)

235 Background: The MD Anderson Clinical and Translational Research Center (CTRC) focuses on Phase I and early Phase II clinical trials and is managing approximately 156 studies annually. This 18-room combined treatment and laboratory unit manages an average of 12,500 research pharmacologic time points and over 3,000 individual shipments yearly. In FY12, 74% of shipments were done on the day of collection (DOC), whereas 26% of the shipments were shipped periodically as required by the corresponding protocol. All studies are monitored at each step for errors - minor (simple DOC label corrections) or major (improper or missed specimen). Activity is analyzed and reported monthly. Methods: In 2010, to ensure accuracy of timing, collection method, proper storage, specimen condition, and destination accuracy, we developed a robust proprietary Oracle-based laboratory tracking system (LabTracker). In addition, we designed an Advanced Research Management and Data Analysis interface (ARMADA) which provides daily step by step protocol guidance using an innovative color-icon touch-screen display of all required protocol activities for patients in the CTRC. LabTracker contains all auditable items required in the clinical trial and markedly reduces work duplication and handwritten data transcription. We hypothesized that this input system would help decrease errors and improve research quality. Results: In FY10 there were 2,506 DOC shipments with an overall error rate of 3.07%. In FY12 errors decreased to 1.31% out of 3,128 DOC shipments. In FY10, there were 14,507 timepoints with 28 major errors (0.19%). In 2012, with 13,490 timepoints, major errors decreased to 19 (0.076%). LabTracker database also supports billing and has catalogued over 275,000 samples. This system provides real-time accounting and has revolutionized the quality control system of the CTRC as well as the research finance component with 98% charge capture efficiency within 30 days. Conclusions: The LabTracker/ARMADA systems are high volume phase I protocol management tools which have improved quality, decreased redundant work, and support a real time financial management system for complex phase I clinical trials.
Multiple utilities of portal vein embolization for patients with hepatocellular carcinoma.
Authors: Toru Beppu, Hirohisa Okabe, Kazutoshi Okabe, Toshiro Masuda, Kosuke Mima, Katsunori Imai, Hiromitsu Hayashi, Koichi Doi,, Akira Chikamoto, Takatoshi Ishiko, Hiroshi Takamori, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

319 Background: Portal vein embolization (PVE) is a multi-potential treatment for hepatocellular carcinoma (HCC). The aim of this study is to identify the efficacies of PVE for resectable and unresectable HCC patients. Methods: Until 2011, 668 HCC patients underwent hepatic resection and 102 HCC patients treated with PVE. PVE was performed with percutaneous and ipsilateral approach using ethanolamine oleate iopamidol. Preoperative future remnant liver volume (%LV) and functional liver volume (%FLV ) were assessed with our developed combined 99m Tc- galactosyl human serum albumin (GSA) scintigraphy (SPECT)/CT system. In unresectable cases chemoembolization (TACE) was repeated after PVE. Results: 1. Comparison of %LV and %FLV after right-PVE (n=40). %FLV before PVE was significantly lower in PVE group (38%) compared to non-PVE group (58%), but increased remarkably after PVE (from 38% to 55%, P &lt; 0.0001). Right hepatectomy was successfully completed in 10 patients based on %FLV, instead of conventional %LV. 2. Long-term prognosis after right-hepatectomy with /without PVE (n=60). The 3- and 5-year disease-free survival (DFS) rates in the PVE group were significantly greater than those in the non-PVE group (78% and 78% versus 20% and 0%, P = 0.01). The 3- and 5-year overall survival (OS) rates in the PVE group were also higher than those in the non-PVE group (72% and 72% versus 57% and 12%, P &lt;0.05). By multivariate analysis, independent prognostic factors for DFS were application of PVE (HR3.59), Multiple tumor (HR3.57), Fibrosis stage F3–4 (HR2.81), and protein induced by vitamin K absence or antagonists-II (PIVKA-II) ≥678AU/ml (HR2.69). 3. Prevention of intrahepatic metastases in unresectable HCCs in hemi-liver (n=40). The 3-year intrahepatic recurrence rates in the non-portal-embolized area was 58.8% and 81.8%, and the 5-year OS was 38.2% and 8.5%, in the PVE/TACE group and TACE group, respectively. The former rates were sinificantly higher (P&lt;0.05). Conclusions: PVE can improve resectability, and might improve disease-free and overall survival for patients with both resectable and unresectable HCC.
Predicting Poor Peripheral Blood Stem Cell Mobilization Using Initial Peripheral CD34 Counts in Patients with Lymphoma.
Authors: Shirshendu Sinha, Shaji Kumar, Dennis A. Gastineau, William Hogan, Francis Buadi, David Dingli, Angela Dispenzieri, Morie A Gertz, Carl Greiner, Suzzane Hayman, David Inwards, Patrick B Johnston, Martha Q. Lacy, Mark R. Litzow, Luis F. Porrata, Jeffrey Winters, Ivana N Micallef
Journal: Blood (2009)
Strategies for introducing outpatient specialty palliative care in gynecologic oncology.
Authors: Casey M. Hay, Carolyn Lefkowits, Marie Bakitas, Megan Crowley-Makota, Renata Urban, Linda R. Duska, Leslie Horn Clark, Stephanie L. Creasy, Yael Schenker
Journal: Journal of Clinical Oncology (2016)

111 Background: Concern that patients will react negatively to the idea of palliative care is cited as a barrier to timely referral. Strategies to successfully introduce specialty palliative care to patients have not been well-described. We sought to understand how gynecologic oncologists introduce outpatient specialty palliative care. Methods: We conducted a national qualitative interview study at six geographically diverse academic cancer centers with well-established palliative care clinics between September 2015 and March 2016. Thirty-four gynecologic oncologists participated in semi-structured telephone interviews focusing on attitudes, experiences, and practices related to outpatient palliative care. A multidisciplinary team analyzed interview transcripts using constant comparative methods to inductively develop and refine a coding framework. This analysis focuses on practices for introducing palliative care. Results: Mean participant age was 47 years (± 10). Mean interview length was 25 minutes (± 7). Gynecologic oncologists described three main strategies for introducing outpatient specialty palliative care: first establish a strong primary relationship and trust with patients in order to alleviate fear and increase acceptance of referral; focus initial palliative care referral on symptom control to gain a “foot in the door”, facilitate early relationship-building with palliative care clinicians, and dissociate palliative care from end-of-life; and normalize and explain palliative care referral to decrease patient anxiety and confusion. These strategies aimed to decrease negative patient associations and encourage acceptance of early referral to palliative care specialists. Conclusions: Gynecologic oncologists have developed strategies for introducing palliative care services to alleviate patient concerns. Future research should examine patient perception of these strategies and assess impact on rates of acceptance of outpatient specialty palliative care referral.