tbuckley/cabot-search huggingface dataset:
Detection of early-stage pancreatic ductal adenocarcinoma (PDAC): Sensitivity, specificity, and discriminatory properties of the serum-based PAM4-immunoassay.
Authors: David V. Gold, Jochen Gaedcke, B. Michael Ghadimi, Michael Goggins, Ralph H. Hruban, Mengling Liu, Guy Newsome, David M. Goldenberg
Journal: Journal of Clinical Oncology (2012)

151 Background: We recently reported that a serum-based enzyme immunoassay employing the PAM4 antibody was able to correctly identify 82% of patients with known PDAC and, importantly, that this assay had promising sensitivity for detecting early-stage disease. We now extend these findings in a much larger patient population that includes over 600 sera from both malignant and benign diseases of the pancreas and surrounding tissues. Methods: In a blinded analysis, sera from patients with confirmed PDAC (N=298), other cancers (N=99), benign disease of the pancreas (N=126), and healthy adults (N=79) were evaluated by enzyme immunoassay for concentration of PAM4-antigen levels. Results: Overall sensitivity for detection of PDAC was 76%, with 64% of stage-1 patients testing positive and a higher sensitivity (85%) for advanced disease. For the most part, sera from patients with neuroendocrine tumors of the pancreas or cancers of other origin (squamous, GIST, etc.) did not have elevated levels of the PAM4-antigen. Approximately half of the patients with ampullary (48%) and extrahepatic biliary (50%) adenocarcinomas had positive levels of circulating PAM4-antigen. Of 126 patients diagnosed with benign conditions of the pancreas, only 24 (19%) were positive and, in particular, 18 of 80 (23%) patients with chronic pancreatitis (CP) were positive. ROC curve analysis demonstrated a statistically significant difference between the PDAC and CP groups (P &lt; 0.0001), with an area under the curve of 0.84 ± 0.02 (95% CI: 0.79 – 0.89). The positive- and negative-likelihood ratios for differentiating PDAC from benign conditions of the pancreas were 4.00 and 0.30, respectively. Conclusions: The PAM4-immunoassay detects nearly two-thirds of stage-1 PDAC patients, and does so with high discriminatory power with respect to benign pancreatic disease. Our results provide a rationale for longitudinal surveillance of patients considered at high-risk for PDAC (e.g., familial pancreatic cancer, new-onset diabetes, etc.) with the PAM4 assay. (Supported in part by NIH grants CA096924, CA120432 and CA62924, and the Turpin Foundation.)
Impact of the intensity of conditioning regimen in 144 patients with follicular lymphoma (FL) receiving a matched unrelated donor stem cell transplant (MUD-SCT): An analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (LWP-EBMT)
Authors: A. Sureda, I. Avivi, C. Canals, J. Maertens, D. Niederwieser, G. J. Mufti, J. Finke, A. Schattenberg, J. J. Cornelissen, H. Tilly, S. Montoto
Journal: Journal of Clinical Oncology (2008)

7036 Background: Matched unrelated donor stem cell transplant (MUD-SCT) provides the only potentially curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. Methods: The data of 144 patients with FL treated with reduced-intensity conditioning (RIC: 93) or conventional myeloablative (CONV: 51) MUD-SCT between 1991 and 2005 and included in the EBMT registry are reported. Results: Median time from diagnosis to MUD-SCT was 46 months and the median number of previous treatment lines was 4, including an autograft in 47% of patients. RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) at 3 years was 34% and 46% for the RIC and the CONV groups, respectively (p<0.001). No differences were found in the risk of recurrence according to the conditioning regimen. Patients receiving a RIC procedure had a significantly longer progression-free survival (3-year PFS: 43%) and overall survival (3-year OS: 49%) than CONV recipients (3-year PFS: 35% -p=0.004-; 3-year OS: 40% -p=0.001-). Conclusions: This study demonstrates that RIC-MUD results, even in heavily pre-treated populations, in a significantly prolonged PFS. No significant financial relationships to disclose.
A population-based assessment of the risk of fragility fracture associated with the use of adjuvant hormone therapy for early breast cancer in older women.
Authors: K. Enright, M. E. Trudeau, N. Taback, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2011)

519 Background: Change in bone density is one of the most commonly reported long-term sequelae of adjuvant hormonal therapy for the treatment of early breast cancer (EBC), although the magnitude and direction of change varies with the type of hormonal therapy. Compared with tamoxifen (TAM), the use of aromatase inhibitors (AI) has been associated with an increased risk of fragility fracture, but it remains unclear how much of this increased risk is attributable to the protective effect of TAM versus the detrimental effects of the AIs. We sought to determine the population based risk of fragility fracture associated with the use of adjuvant hormonal therapy using linked administrative databases in older women with EBC compared with non-cancer controls. Methods: All incident EBC patients >66y diagnosed between Jan/01-Dec/08 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to multiple provincial healthcare databases to provide comprehensive medical follow-up. Two treatment cohorts were identified based on the use of either TAM (5,704) or AI (4,760). Using a propensity score matching method, a non-cancer control group was created for both the TAM (n = 16,322) and AI (n = 13, 063) cohorts. Cox proportional hazard models were used to determine the association between each hormone therapy and the development of a fragility fracture. Results: After a median observation time of 5.1 years for TAM, and 2.8 years for AI, 11.5% of the TAM and 7.5% of the AI users developed a fragility fracture. Compared with matched controls (Table), TAM users had a significantly lower adjusted risk of fracture, while AI users had a higher risk. Conclusions: Fragility fractures are a concern in older women with EBC on adjuvant hormone therapy, and bone health should be monitored closely, particularly with the use of AIs. Hazard ratio (HR) for fragility fracture associated with hormone therapy for EBC. Group N Fragility fractures (%) HR 95% CI P value Tam 5,704 647 (11.5%) 0.91 0.83–0.99 0.03 Tam non-cancer control 16,322 2,115 (13.0%) 1.00 AI 4,760 356 (7.5%) 1.12 0.99–1.26 0.07 AI non-cancer control 13,063 963 (7.3%) 1.00
The extended care unit: A feasible economic solution for longer-term palliative inpatients.
Authors: Aaron Kee Yee Wong
Journal: Journal of Clinical Oncology (2016)

143 Background: Many inpatient palliative care units (PCUs) in Australia require patients who cannot go home, but remain stable after 2 weeks, to be discharged to nursing homes (NHs). This involves moving between 5 locations (home, acute hospital, PCU, NH transition bed, NH), in the final weeks of life. We propose an “Extended Care Unit” (ECU) to avoid unnecessary moves for such patients. This study aimed to investigate the feasibility of the proposed ECU, including identifying demand, admission criteria, length of stay, and hospital costs. Methods: Using a retrospective, observational design, we censored all inpatients on a single day from the largest tertiary referral centre in the state. 475 files were reviewed. ECU admission criteria used were: prognosis &lt; 90 days, unable to return home, and NH referral process commenced. Two predictive mortality scores were calculated. Total cost was calculated based on average bed cost over 12 months. ECU bed costs were based subacute aged care bed costings. Results: Fifteen (3%) patients met ECU admission criteria. 80% (n = 12) died within 90 days. 60% were transferred between ≥ 4 places. After fulfilling ECU admission criteria, a further 279 acute and PCU bed days were used. If an ECU were available, hospitals would save $207.70 per patient per bed day. Conclusions: The ECU model is a feasible economic solution for this demographic of patients whose needs are currently poorly met. We provide evidence of clear demand, with significant cost savings. Effective admission criteria to identify suitable patients for the ECU are also proposed.
Genetic Disruption of Rac1 but Not Rac2 Is Sufficient To Ameliorate the Development of Juvenile Myeloproliferative Myeloid Leukemia in Nf1−/− Mice.
Authors: Fengchun Yang, Jayme Allen, Shi Chen, Yan Li, Jin Yuan, Waylan Bessler, David A. Ingram, D. Wade Clapp
Journal: Blood (2006)
Breast cancer characteristics among Hispanic women from a Southwestern county hospital.
Authors: M. N. Kundranda, S. Amar
Journal: Journal of Clinical Oncology (2011)

1600 Background: Hispanic women in the US have a lower incidence but higher mortality from breast cancer (BC). Data is limited describing the disease in Hispanics. We describe our experience among BC patients (pts) in a county hospital serving an indigent population; majority of whom are of Hispanic ethnicity. Methods: Retrospective observational study, N==359 pts diagnosed with BC from 2005-2009. Metastatic disease and non-hispanic minority were excluded. Patient characteristics included demographics, pathology (histology, stage, grade and tumor size), hormone status (ER, PR and HER-2) and Rx (surgery, radiation (RT) and hormonal therapy). Pearson’s chi-square test and student’s t-test was used to compare categorical and continuous variables respectively. Results: Study cohort = 199 (79%) Hispanic (H) and 53 (21%) Caucasian (C). H were younger at diagnosis; mean age 50.4 vs 54.3 (C) (p=0.298). Most common histology was infiltrating ductal carcinoma. No significant difference in pathological charecteristics was noted. We observed higher % of hormone receptor + in H (ER+; 75 vs 68% and PR+; 70 vs 66%). HER-2 + was higher in the H (16 vs 14.5%). Triple negative (TN) BC was higher in the H (20 vs 11%, p=0.28). Higher % of H had surgery (86 vs 74%; p=0.03); however, fewer H received RT after lumpectomy (22 vs 47%; p=.01) In premenopausal pts a higher % of H received tamoxifen (45 vs 27%; p=0.27). A higher % of AI use was noted in the post menopausal H (27 vs 22%; p=0.58). Screening mammogram (SM): 69% had no SM. H vs C (73 vs 80%). Among the whole cohort 40% were lost to follow-up. Median follow-up was higher in H (29 vs 20 months, p=0.03). Mortality rates were not statistically significant (H vs C; 2 vs 3.7%). Conclusions: Prior studies report a higher mortality from BC among H vs C women. However, our analyses from a large county hospital demonstrated statistically similar mortality rates in H compared to C. This is despite H presenting earlier and having more TN tumors. This observation could be attributed to similar socioeconomic status in these patients irrespective of ethinicity seeking care in this county hospital. Larger studies need to be done to tease out biological vs. socioeconomic influences in the mortality related to BC among Hispanic women.
UGT1A1*28 genotype–driven phase II study of irinotecan and doxifluridine (5'-DFUR, an intermediate form of capecitabine) for metastatic colorectal cancer.
Authors: S. Kanekiyo, S. Hazama, R. Shimizu, H. Ozasa, T. Yamamoto, S. Yoshino, N. Okayama, Y. Hinoda, M. Oka
Journal: Journal of Clinical Oncology (2011)

e14074 Background: We reported at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of irinotecan and 5'-DFUR for metastatic colorectal cancer (CRC). The recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes of biweekly irinotecan administration was 150 mg/m2 for patients (pts) with wild *1/*1 and 70 mg/m2 for mutated *1/*28. Now we presented *28 oriented P II study based on this RD. We evaluated efficacy and safety of irinotecan and 5'-DFUR. Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0-1, age<80, adequate organ functions, and written informed consent. Twenty one pts with wild genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m2 for pts with *1/*1 genotype and 70 mg/m2 for *1/*28. In this study the primary endpoint is response rate (RR) and the secondary endpoints are overall survival (OS), time to treatment failure (TTF) and drug induced toxicities. Results: Twenty eight pts were included in this study. Twenty two pts were wild *1/*1 genotype and six pts mutated genotype. In all, six pts had partial responses and RR was 21.4% (6/28). In the mutated genotype, one pt had partial responses and RR was 16.7% (1/6). Median OS was 15.2 months and median TTF was 4.4 months. The most common drug induced grade (G) 3-4 toxicities (wild vs mutant) were diarrhea (11% vs 0%), appetite loss (7% vs 16.7%), general fatigue (4% vs 0%), nausea (4% vs 16.7%) and neutropenia (14.3% vs 0%). Conclusions: RR was about 20% and similar in both wild and mutated genotype. The G3-4 adverse events were about 15% and everything controllable. Global standard intensive chemotherapy for colorectal cancer has been established around the world. This polymorphism oriented regimen can be useful for pts with poor performance status or for elderly patients.
The role of LDH serum levels in predicting global outcome in patients with HCC undergoing TACE: Implications for clinical management.
Authors: Maristella Bianconi, Luca Faloppi, Mario Scartozzi, Riccardo Giampieri, Elena Maccaroni, Alessandro Bittoni, Michela Del Prete, Cristian Loretelli, Laura Belvederesi, Gianluca Svegliati Baroni, Stefano Cascinu
Journal: Journal of Clinical Oncology (2012)

326 Background: In many tumor types serum LDH levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. However data about HCC are lacking particularly in the clinical setting of patients undergoing transarterial-chemoembolization (TACE) in whom hypoxia and neo-angiogenesis may represent a molecular key to treatment failure. Aim of our analysis was to evaluate the role of lactate dehydrogenase (LDH) pre-treatment levels in determining clinical outcome for patients with HCC receiving TACE. Methods: One-hundred and fourteen patients were available for our analysis. For all patients LDH values were collected within one month before the procedure. For study purposes we divided our patients into two groups, according to LDH serum concentration registered before TACE (first group: LDH ≤ 450U/l 84 patients; second group: LDH &gt; 450U/l 30 patients). Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased: 62 patients vs decreased 52 patients). Results: Patients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values below 450 U/l median time to progression (TTP) was 16.3 months, whereas it was of 10.1 months in patients above the cut-off (p=0.0085). Accordingly median overall survival (OS) was 22.4 months and of 11.7 months (p=0.0049). In patients with decreased LDH values after treatment median TTP was 12.4 months, and median OS was 22.1 months, whereas TTP was 9.1 months and OS was 9.5 in patients with increased LDH levels (TTP: p=0.0087; OS: p&lt;0.0001). Conclusions: In our experience, LDH seemed able to predict clinical outcome in terms of TTP and OS for HCC patients undergoing TACE. Given the correlation between LDH levels and tumour angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for clinical trial exploring a multimodality treatment approach with TACE and anti-VEGF inhibitors in order to improve TTP and OS.
End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation for prostate cancer.
Authors: Phuoc T. Tran, Amol Narang, Ashwin Ram, Scott P. Robertson, Pei He, Emiliy Griffith, Harleen Singh, Tate DeWeese, Stephanie Honig, Todd R. McNutt, Danny Song, Theodore L. DeWeese
Journal: Journal of Clinical Oncology (2015)

68 Background: In patients with localized prostate cancer undergoing radiation therapy (RT) +/- androgen deprivation therapy (ADT), an end of radiation (EOR) PSA obtained during the last week of RT may serve as an early post-treatment predictor of poor outcomes and identify patients in whom to pursue treatment intensification or novel therapies. Methods: We reviewed an IRB-monitored, prospectively acquired database of patients with prostate cancer treated with definitive RT at our institution from 1993-2007 (n=890). Patients with an available EOR PSA were divided into two cohorts and analyzed separately based on inclusion of ADT into the treatment regimen. EOR PSA thresholds of 0.5 ng/mL and 1.0 ng/mL were explored. Multivariate analysis was performed to determine prognostic factors for biochemical failure-free survival (BFFS, Phoenix criteria) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA thresholds. Results: Median age was 69 years, with an even distribution of NCCN low risk (33.5%), intermediate risk (34.0%), and high risk (32.5%) patients. Median RT dose was 7020 cGy, and 54.5% were treated with ADT. Median follow-up of the entire cohort was 11.7 yrs. EOR PSA level was available for the majority of patients (77.5%). On multivariate analysis, EOR PSA &gt;0.5 ng/mL was significantly associated with worse BFFS (p&lt;0.0001) and OS (p&lt;0.0001). In the subset of patients undergoing RT with ADT for NCCN intermediate/high risk disease, 5 yr BFFS was more disparate based an EOR PSA threshold of 0.5 ng/mL (5 yr BFFS: 87.3% vs. 41.1%, p&lt;0.001), than initial NCCN risk level (5 yr BFFS: 88.7% vs. 76.9%, p=0.038). In NCCN low risk patients undergoing definitive RT alone, an EOR PSA threshold of 1.0 ng/mL was significantly prognostic of outcome (5 yr BFFS: 100.0% vs. 88.6%, p=0.024). Conclusions: For NCCN intermediate/high risk patients undergoing RT with ADT, EOR PSA &gt;0.5 ng/mL may represent a better surrogate for poor outcomes than initial risk group. In addition, NCCN low risk patients undergoing RT alone who obtained an EOR PSA ≤1.0 ng/mL experienced excellent BFFS. Prospective evaluation of the utility of EOR PSA should be explored.
Phase II randomized study of preradiation treatment with temozolomide (TMZ) and bevacizumab (BEV) previous to TMZ plus radiation plus BEV versus the same treatment without BEV therapy in unresectable glioblastoma (GB): GENOM 009.
Authors: C. Balana, O. Gallego, J. M. Vieitez, R. De Las Penas, A. Herrero, S. Peralta, R. Luque, M. Gil, S. Villa, O. Etxaniz, C. Carrato, J. Sepulveda
Journal: Journal of Clinical Oncology (2011)

e12519 Background: Unressectable GB hardly benefits from standard treatment. Patients frequently deteriorate neurologically during radiotherapy. An effective pre-radiation treatment might improve their prognosis and allow them to complete concomitant radiotherapy and temozolomide treatment. Bevacizumab in recurrent HGG displays high objective responses. Methods: We are conducting a phase II, two arms, open label, randomized, multicentric study with 2 cycles of temozolomide before radiation therapy and concomitant temozolomide plus maintenance in patients with GB and ‘biopsy-only’ (Arm A). Bevacizumab is added to one arm during the neo-adjuvant and concomitant phase (Arm B). Ninety patients will be randomized Primary endpoints: response rate after neoadjuvant treatment (RANO criteria). Secondary endpoints: differences between arms in PFS, completion of radiotherapy, toxicity, maintenance of neurological status and overall survival We present here the previously planned results of a security analysis after the inclusion of the first 10 patients treated with bevacizumab. Results: After the inclusion of 22 patients: 2 patients were not evaluable and 10 patients were treated in each arm. Arm A: 3 adverse events: 1/10p hematological grade 4 toxicity in the neo-adjuvant phase, 2/10p lung embolism all solved with treatment. From these patients 6/10 completed neo-adjuvant and concomitant phase, 2/10 completed only neo-adjuvant phase and 2/10 progressed without completing neo-adjuvant phase. Arm B: 2 adverse events: 1 pneumonia grade 3 and 1 p with hypertensive crisis grade 2 all solved with treatment. From these patients, 7/10 p completed neo-adjuvant and concomitant treatment, 2/10 completed neo-adjuvant treatment and 1/10 progressed without completing neo-adjuvant phase Conclusions: The trial is ongoing as the security analysis was acceptable.
Surgical lymph node clearance and pathologic evaluation in gastric cancer.
Authors: A. G. Khattak, J. C. Sachdev, M. C. Evangelist, J. Denbo, W. S. Orr, M. Ul-Haq, A. Farooq, A. C. Thompson, R. A. Dilawari, R. U. Osarogiagbon
Journal: Journal of Clinical Oncology (2011)

131 Background: Lymph node (LN) metastasis is common in gastric cancer, with survival implications. The number of LN with metastasis determines pathologic nodal stage; optimal staging requires examination of &gt;14 LN. This requires adequate surgical LN clearance and careful pathology evaluation. Sub-optimal LN examination may be due to surgical or pathology laboratory quality problems, affecting the rational implementation of corrective measures. We evaluated LN examination practice in our community. Methods: Review of all gastric resections at two hospital systems in Memphis, TN from 1999 to 2008, excluding patients with pre-operative chemo/radiation therapy. Two surgeons separately reviewed all operation reports for details of LN station clearance. We tested concordance between surgeons by the kappa statistic (k) and correlated surgeon reports of LN clearance to the number of examined LN in the pathology report. Results: 51% of 116 operative reports did not state LN stations resected. The concordance rate between the two surgeons was high (k score per station ranging from 0.66 [very good] to 1.0 [perfect]). The median number of LN stations cleared was similar after proximal (PG) and distal gastrectomy (DG), but significantly more after total gastrectomy (TG) (p&lt;0.0001). Only 39% of patients had &gt;14 LN examined, 6% had none. The number of LN examined was lowest for PG, intermediate for DG and highest for TG patients (Table). There was no correlation between number of surgically cleared LN stations and number of examined LNs (Spearman correlation coefficient 0.23). Conclusions: Operating surgeons frequently did not identify a LN dissection procedure. Fewer LN were retrieved by pathologists during examination of PG specimens although the surgeon-reported LN clearance was similar between PG and DG. The lack of correlation between LN stations cleared and number of LN examined suggests inadequate pathological examination of LNs submitted in surgical specimens. [Table: see text] No significant financial relationships to disclose.