tbuckley/cabot-search huggingface dataset:
The risk-based STHLM3 model to improve prostate cancer testing in men 50-69 years: Further health, economic, and clinic evaluation.
Authors: Henrik Gronberg, Jan Adolfsson, Markus Aly, Tobias Nordström, Peter Wiklund, Yvonne Brandberg, James Thompson, Fredrik Wiklund, Johan Lindberg, Mark Clements, Lars Egevad, Martin Eklund
Journal: Journal of Clinical Oncology (2016)

36 Background: Prostate-specific antigen (PSA) is used to screen for prostate cancer but suffers from a high false-positive rate that translates into unnecessary prostate biopsies and over-diagnosis of low-risk prostate cancers. We aimed to develop a model for prostate cancer screening with better test characteristics than PSA. Methods: STHLM3 is a prospective, population-based, paired screen-positive diagnostic study. It investigates whether the predefined STHLM3 model, a combination of 6 plasma protein biomarkers (PSA, free-PSA, intact-PSA, HK2, MIC-1, and MSMB), genetic polymorphisms (232 SNPs), and clinical variables (age, family history, previous biopsies, DRE, and prostate volume) can substantially reduce the proportion of men biopsied while maintaining the same sensitivity to diagnose Gleason score ≥ 7 prostate cancer as PSA ≥3 ng/ml. In addition, a health economic evaluation was performed comparing the STHLM3 model with current clinical practice in Stockholm. Results: 58,818 men without prostate cancer aged 50-69, participated in the STHLM3 study, with 6,700 undergoing subsequent prostate biopsy. The STHLM3 model performed significantly better (p&lt;0.001) than PSA for detecting GS ≥7 cancers, increasing the Area Under the Curve from 0.56 to 0.74. All variables used in the STHLM3 Model were significantly associated with Gleason score ≥7 prostate cancers (p&lt;0.05) in a multiple logistic regression model. Using the same sensitivity as PSA ≥3 ng/ml to diagnose Gleason score ≥7 prostate cancer, the STHLM3 model reduced the number of biopsies by 32% (95% CI 24%-39%) and avoided 44% (95% CI; 35%-54%) of the negative biopsies. The number of Gleason score 6 cancers was reduced by 17% (95% CI; 7%-26%). Positive ICER for the STHLM3 model was seen in all models of the health economic analysis. Conclusions: The STHLM3 model reduces unnecessary biopsies without compromising the ability to diagnose Gleason score ≥7 prostate cancer in a cost-efficient way. This is a significant step towards personalized risk-based prostate cancer diagnostic programs. Clinical trial information: ISRCTN84445406.
Risk stratification and stage migration effect of novel imaging and biomarker technology in men with biochemical failure after local therapy for prostate cancer.
Authors: B. B. Desai, D. I. Quinn, C. I. Piatek, R. Tang, J. Hu, A. Goldkorn, M. E. Gross, D. Hawes, H. Jadvar, T. B. Dorff
Journal: Journal of Clinical Oncology (2011)

e15196 Background: To evaluate the diagnostic utility of combined PET/CT imaging with 18F-NaF, 18F-FDG and circulating tumor cells (CTCs) in early detection and localization of metastatic disease in men with treated localized primary prostate cancer who present with biochemical failure (PSA relapse) and negative standard imaging tests. Methods: As part of an IRB-approved prospective imaging trial, 27 prostate cancer pts (71.5 ± 8.6 yrs) with PSA-relapse (med 3.24, R 0.57-238 ng/ml) after curative local therapy (18 RP, 9 EBRT; Gleason score 7±1) underwent both 18F-NaF (10.38 ± 1.09 mCi) and 18F-FDG (14.46 ± 0.85 mCi) PET/CT scans on 2 separate days within 1 week. 8/27 pts in the PET trial were concurrently enrolled on a phase II trial of a combination herbal therapy and analyzed for CTCs using a micro fluidics collection device. Treatment-specific AUA and ASTRO consensus definitions of PSA relapse defined eligibility for both trials. Cross tabulation compared concordance between the results of CTC and imaging studies. Results: 12 of 27 men (44.4%) with PSA relapse and negative/equivocal standard imaging scans had positive imaging studies for distant skeletal/soft tissue metastasis on at least 1 of PET/CT scans; 4 positive on both scans, 6 positive only on 18F-NaF, 2 positive only on 18F-FDG. Of 23 pts in the phase II, 5 had detectable CTCs. Both imaging and CTC data were available on 8 pts. Cross tabulation of CTC and PET/CT studies showed, 2 concordant positive cases, and 3 discordant cases (1 CTC positive only and 2 PET/CT positive only) with the remaining 3 cases negative on both imaging and CTC. Conclusions: Novel diagnostic techniques including 18F-NaF, FDG PET/CT scans and CTC assessment may detect occult metastatic disease in around 40% of men with PSA relapse. These novel imaging and biomarker modalities may enhance the ability of clinical information (PSA kinetics, Gleason score, etc.), to risk-stratify men with biochemical recurrence of prostate cancer and may lead to a stage migration effect in this disease state. 18-F NaF PET F-18 FDG and F-18 NaF PET/CT Negative Positive Total Negative Positive Total Negative 15 6 21 Negative 3 2 5 Positive 2 4 6 Positive 1 2 3 18F-FDG PET Total 17 10 27 CTC study Total 4 4 8
Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: 3-Day IV/oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving highly emetogenic chemotherapy (HEC)
Authors: J. Strausz, J. Rolski, Z. Aziz, M. E. Guckert, O. Wright, R. R. Bandekar, S. Thorn, P. Wissel, J. Herrstedt
Journal: Journal of Clinical Oncology (2008)

20585 Background: In a phase II dose-ranging trial, casopitant, a novel NK-1 receptor antagonist, demonstrated efficacy in preventing CINV in pts receiving HEC. Here we present results of a 3-day IV/oral regimen of casopitant added to ondansetron/dexamethasone (OND/DEX) for the prevention CINV events in pts receiving HEC. Methods: This multinational, double-blind, active-controlled trial included 810 pts with 99% of pts receiving cisplatin-based chemotherapy (up to 6 cycles). Pts were randomized to a 3-day IV/oral dose arm (casopitant 90 mg IV + OND 32 mg IV + DEX 12 mg PO) on D1 plus casopitant 50 mg PO D2–3 + DEX 8 mg PO QD D2–4, or either a single dose casopitant arm (150 mg PO + OND 32 mg IV + DEX 12 mg PO) on D1, or no additional therapy (CTRL; OND 32 mg IV + DEX 20 mg PO) on D1 plus DEX 8 mg PO BID D2–4. Complete Response (CR; no vomiting/retching, rescue medications) in the first 120 hrs of HEC was the primary endpoint. Results: A statistically significant improvement (at a 2.5% level of significance adjusted for two primary comparisons) in CR rate in cycle 1 compared with CTRL was observed. This clinical benefit appeared to be maintained for up to 6 cycles. Significant improvements were observed in CR in the acute and delayed phases, as well as in vomiting, during cycle 1. Clinically meaningful improvements in the reported secondary endpoints of no significant nausea (SN), and no nausea were also observed. Casopitant was generally well tolerated. AE frequency was similar across the arms, with neutropenia, leukopenia and anemia being the most frequent. Conclusions: In pts receiving HEC, a 3-day IV/oral regimen of casopitant added to OND/DEX demonstrated a clinically meaningful reduction in CINV events. This benefit appeared to be maintained through repeat cycles. This regimen was generally well tolerated over all cycles. Cycle of HEC Endpoints (0–120 hrs) CTRL n=265 (%) 90 mg IV D1 + 50 mg PO D2–3 n=269 (%) P-value 1 Complete Response 175 (66) 214 (80) 0.0004 Acute CR (0 - 24 hrs) 234 (88) 253 (94) 0.0165 Delayed CR (24–120 hrs) 175 (66) 214 (80) 0.0004 No vomiting/No significant nausea (VAS <25 mm)/No nausea (VAS <5 mm) 179 (68)/184 (69)/121 (46) 222 (83)/205 (76)/147 (55) 0.0001/0.07 40/0.0356 2 Complete Response 113/146 (77) 143/161 (89) NA 3 Complete Response 92/118 (78) 106/122 (87) NA 4 Complete Response 66/89 (74) 67/76 (88) NA 5 Complete Response 13/15 (97) 5/6 (83) NA 6 Complete Response 5/9 (56) 3/5 (60) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Low rates of cancer-directed surgery for pancreatic adenocarcinoma despite favorable patient demographics and tumor stage.
Authors: A. M. Kaminski, P. T. Silberstein
Journal: Journal of Clinical Oncology (2011)

e14600 Background: Previous studies have utilized the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry to evaluate factors affecting rates of utilization of cancer directed surgery (CDS) through 2002. This is the first study to add 2003-2007. Methods: SEER was used to evaluate trends in utilization of CDS for patients diagnosed with pancreatic adenocarcinoma from 1988 to 2007. Univariate analyses were used to compare surgical data, tumor stages, years of diagnosis, and selected patient demographics, race, age, and marital status. Results: 56,956 patients diagnosed with pancreatic adenocarcinoma between 1988 and 2007 were identified. 20,385 (35.8%) were classified as localized or regional disease. In 1988, 19.5% (95) of these patients underwent CDS, this increased to 41.5% (275) in 1998 and decreased to 29.2% (557) in 2007. Localized or regional stage, younger age, white race, and married status were associated with higher utilization of CDS. Gender differences were insignificant. White, married patients under age 60 with localized disease had the highest rate of CDS, 49.1%. Of the patients in this demographic who did not undergo CDS, 78.2% did not have it recommended, 7.5% had contraindications, 2.0% refused CDS, and 10.2% had unknown reasons. CDS in this demographic is associated with significantly higher 1 and 5 year survival rates than not having surgery (CDS 1 year 76.8%, 5 year 34.2%; Non-CDS 1 year 39.7%, 5 year 3.5%). Conclusions: Rates of CDS for pancreatic adenocarcinoma fluctuated between 1988 and 2007, rising modestly in aggregate, but remaining low. Most recently, only approximately 30% of patients with localized or regional disease got surgery. It might be expected that these rates would be higher, especially for young patients with localized disease. However, even among patients with the most favorable demographic and stage profiles, over half do not undergo CDS, mostly because it is not recommended by the health care team. Those who do undergo CDS have a significant survival advantage. Further investigation should be done to determine the appropriateness of not operating on the majority of potentially resectable pancreatic cancer.
Long-term results of expandable endoprosthesis replacement in children with malignant bone tumors.
Authors: W. Woźniak, I. Ługowska, A. Szymborska
Journal: Journal of Clinical Oncology (2010)

9553 Background: In children undergoing resection for malignant bone tumors the use of expandable endoprostheses allows for correction of limb length discrepancy. The aim of this study was to analyze long-term results of expandable endoprosthesis replacement in a consecutive series of children with malignant bone tumors treated in one institution. Methods: Of over 300 limb-salvage procedures performed for musculoskeletal tumors between 2000 and 2009, 78 patients underwent expandable replacement of the distal femur and proximal tibia (47 invasive and 31 non-invasive systems). Patients characteristics: 43 males, 35 females; a mean age of 12 years; diagnosis: osteosarcoma - 57 patients, Ewing's sarcoma - 18 patients, other malignant bone tumors - 3 patients. All patients underwent chemotherapy and wide resection of bone tumor with placement of endoprosthesis. Outcome measures included surgical/oncological complications; elongation-related complications, endoprosthesis damage and functional status assessment. Results: At a median follow-up of 5 years (range: 9 months - 10 years) surgical complications occurred in 22 patients (28%) and local recurrence in 6 (7.7%). Treatment of complications included endoprosthesis re- implantation (7 patients), surgical revision (7 patients), amputation (5 patients) and conservative management (9 patients). The limb elongation was performed in 32 patients (a total of 40 procedures). Complications after elongations occurred in 6 patients (15%) and included infections (5%) and flexion/extraction contractions (10%). All complications took place following invasive endoprosthesis replacement and required surgical revision. Four of 31 patients (13%) developed endoprosthesis damage; all these cases included non-invasive systems and necessitated endoprosthesis replacement. Final functional status of the limb endoprosthesis was excellent/good in 81% patients, moderate in 10% and poor in 9%. Conclusions: Reconstruction with an expandable endoprosthesis provides long-term satisfactory results in pediatric patients with malignant bone tumors. No significant financial relationships to disclose.
A phase IIb, randomized, controlled, multicenter, open-label study of the efficacy and immune response of GVAX pancreas vaccine and CRS-207 compared to chemotherapy or to CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE Study).
Authors: Dung T. Le, Andrea Wang-Gillam, Vincent J. Picozzi, Todd S. Crocenzi, Michael Morse, Herbert Zeh, Robert Lance Fine, Aimee Murphy, Justin Skoble, Ed Lemmens, Sandy Ferber, Allan Rosen, John J. Grous, Thomas Dubensky, Dirk G. Brockstedt, Eric Lutz, Elizabeth M. Jaffee
Journal: Journal of Clinical Oncology (2015)

TPS489 Background: A prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing activity in patients with metastatic pancreatic adenocarcinoma (PDA). GVAX is composed of lethally-irradiated, allogeneic pancreatic cancer cells modified to express GM-CSF. GVAX induces a response against multiple tumor antigens and is given after low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and stimulates both innate and adaptive immunity by activating T cells and NK cells. Results from a phase 2 study demonstrated CY/GVAX plus CRS-207 improved overall survival (OS) compared to CY/GVAX alone (p-value&lt;0.05; Le, GI ASCO 2014). Methods: This is a phase 2b study comparing CY/GVAX and CRS-207 to chemotherapy or to CRS-207 alone in patients with previously-treated metastatic PDA. Patients will be enrolled in two cohorts: 150 patients into a primary cohort of patients with at least two prior chemotherapy regimens for metastatic disease (third + line) and 90 patients into an exploratory cohort of patients with only one prior chemotherapy regimen for metastatic disease (second line). Patients will be randomized in a 1:1:1 ratio to receive 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm A), six doses of CRS-207 (Arm B) or physician’s choice of single-agent chemotherapy (Arm C). The primary objective is to compare OS between Arms A and C in the primary cohort. Secondary/exploratory objectives include: comparison of OS in both primary and exploratory cohorts between all treatment arms, assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with clinical responses. Updated enrollment will be reported. (Sponsor: Aduro BioTech, Inc.; NCT02004262). Clinical trial information: NCT02004262.
The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx.
Authors: Lauren Carcas, Jessica Macintyre, Jaime R. Merchan, Peter Joel Hosein, Ikechukwu Immanuel Akunyili, Maria Restrepo, Monica T. Garcia, Lorraine Portelance, Danny Sleeman, Joe U Levi, Caio Max S. Rocha Lima
Journal: Journal of Clinical Oncology (2015)

460 Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining &gt;25% CDX2 = I, &gt;25% MUC5 = Ga, &gt;25% CDX2 and MUC5 = I/G, &gt;25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for the other histologic subtypes, response to F or G was only analyzed in the 35 metastatic pts with the Ga subtype. 14 were metastatic at diagnosis. 24 males. Median age 57. 21 Hispanic, 14 Non-Hisp. The PFS for Ga treated with F based tx (&gt;12 m) versus G (~9 m) based tx in the 1st line approached statistical significance (p=0.050). In multivariable analysis with adjustments for clinical stage, ECOG, age at dx, there was a significant lower risk of progression in pts treated with F based tx versus G based tx (HR=0.278, p=0.0315). Conclusions: There was near statistical significance favoring F based tx over G based tx in PDAC Ga subtype (p=0.05). Historically, G has proven superior to F as a single agent but our findings suggest F in combination may be superior to G in combination, at least for the treatment of Ga subtype.
Large retroperitoneal lymph nodes (RPLN) as a predictor for venous thromboembolism (VTE) in patients (pts) with germ cell tumor (GCT) receiving first-line chemotherapy (chemo).
Authors: Ben Tran, Malcolm J. Moore, Eitan Amir, Michael A Jewett, Lynn Anson-Cartwright, Jeremy F. G. Sturgeon, Peter W. M. Chung, Padraig Richard Warde, Philippe Bedard
Journal: Journal of Clinical Oncology (2012)

332 Background: VTE causes significant morbidity and mortality in GCT pts. While an existing and validated predictive model identifies VTE risk in chemo pts with any cancer (Khorana model), a predictive model specific to GCT does not exist. Many GCT pts present with bulky RPLN that produce venous stasis in the lower extremities. The objective of this study was to explore the association between large RPLN and VTE in GCT pts receiving chemo and compare large RPLN as a predictor for VTE in GCT pts to the non-GCT specific Khorana model. Methods: Clinical data from our institutional GCT database was complemented by review of radiology, pharmacy and medical records. All GCT pts receiving 1st line chemo between 1-Jan-00 and 31-Dec-10 were included. Large RPLN were defined as ≥5cm in maximal diameter. Factors used in the Khorana model (baseline BMI, hemoglobin, white cell count and platelets) were collected. We compared the predictive accuracy of large RPLN versus Khorana score ≥3 using receiver operator characteristic (ROC) curve statistical analyses. Results: The cohort consisted of 260 GCT pts, median age 31.5 years, predominantly testis primary (235, 90%) and good risk (171, 66%). 17 (7%) developed VTE prior to the start of chemo. 19 (7%) were given prophylactic anticoagulation, none of whom developed VTE. Of the remaining 224 pts, 20 (9%) developed VTE during chemo. In a univariate analysis, large RPLN was strongly associated with VTE (OR 7.74, p&lt;0.001), as were Khorana score ≥3 (OR 9.81, p&lt;0.001) and hospital admission during chemo (OR 3.96, p=0.004). ROC curve analyses demonstrated large RPLN was a significant individual predictor for VTE (AUC 0.588, p=0.03), however, Khorana score ≥3 was a better predictor (AUC 0.664, p=0.02). Adding large RPLN to create a modified Khorana score provided marginal gains (AUC 0.682, p=0.02). Conclusions: Although large RPLN at diagnosis predicts for VTE in GCT pts, the Khorana predictive model is superior. Given the high rate of VTE in GCT pts receiving chemo, we recommend prophylactic anticoagulation for pts at increased risk, including pts with Khorana score ≥3, pts requiring hospital admission or pts with large RPLN.
A phase I-trial of the HIV protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer
Authors: T. B. Brunner, M. Geiger, G. G. Grabenbauer, T. S. Mantoni, A. Cavallaro, R. Sauer, W. Hohenberger, W. G. McKenna
Journal: Journal of Clinical Oncology (2008)

4632 Background: Preclinically, HIV Protease Inhibitors (HPIs) radiosensitized tumours with activated PI3-kinase/Akt pathway. We determined the tolerance of nelfinavir with chemoradiation for patients with locally advanced pancreatic cancer (LAPC). Methods: Patients with histologically proven LAPC were eligible. Oral nelfinavir (2 x 1250 mg) was started 3 days before and continued throughout chemoradiation to 50.4 Gy (boost 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested, 6 patients each: 200 mg/m2 and 300 mg/m2 on days 1, 8, 22, and 29. MTD was defined as DLT occurring in 1/3 or 2/6 patients. DLT was defined as Grade 4 hematologic toxicity or nonhematologic toxicities of ≥ Grade 3 during treatment or within 4 weeks after completion unless clearly attributable to other clinical causes (e.g. stent occlusion). The MTD was defined as the dose of gemcitabine associated with DLT occurring in 33% of the patients treated at the same DL, and the recommended phase II dose (RPTD) was defined as the DL below the MTD. Cisplatin was administered on the same days at 30 mg/m2. Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging PET/CT and CA19–9 levels served to assess response, and responding tumors were resected. Results: Per DL, 5/6 patients received full treatment. Two patients dropped out, one because of clinical depression (DL1) and one with peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) due to biliary stent occlusion and acute cholecystitis due to peritoneal metastasis (DL2). Stent occlusions led to DLT grade 3 liver enzyme and bilirubin elevations (2 patients DL1, 1 patient DL2). Grade 3 nausea/vomiting occurred in a DL2 patient and weight loss in a DL1 patient who refused supportive feeding. DL2 was determined as Recommended Phase Two Dose. Secondary complete resection was possible in 6/10 fully treated patients, and one tumor was pathologically sterilized. Partial CT-responses were observed in 5/10 fully treated patients. PET-responses were complete in 5/9, partial in 2/9. No PET-response was seen in 2/9 evaluable patients. Conclusions: Combined nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with LAPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche