tbuckley/cabot-search huggingface dataset:
Liver resection and outcome of hepatocellular carcinoma (HCC) in a transplant center.
Authors: Afsaneh Barzi, Shu Cao, Yuri Genyk, Jeffrey Kahn, Melissa A Wallman, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2015)

350 Background: HCC has rising incidence and mortality in the US. Liver transplantation and surgery are the definitive treatment options. The median time to liver transplant in California is longer than many other regions. Given the expertise of our surgeons in liver resection we investigated the outcome of HCC at our institution. Methods: We extracted Norris Cancer registry data for patients (pt) with diagnosis of HCC from 2000 to 2010 who received their initial treatment at our facility. Overall survival (OS) is the primary end point of this study. We classified pt into transplant candidates (TC) vs. non-transplant candidates (NTC) based on the combination of T stage and vascular involvement. Results: We identified a total of 497 pts with HCC (Table). 98 pts had incomplete staging and 20 had metastatic disease and excluded from the analysis. We classified 221 pts as TC and 158 pts as NTC. The median OS for the TC was 2.9 years (yr) (95% CI 2.1-3.9) and in the NTC was 1.4 yr (95% CI 1.1 – 1.6). Amongst TC, 44 received transplant, 33 had surgical resection, and 144 had loco-regional treatment. Transplant recipients had an OS of 9.7 yr versus 4.3 yr (95% CI 1.9-9.1) in surgical patients, those with no definitive treatment had a OS of 1.8 yr (95%CI 1.6 -2.3). Among TC Hispanics had the best OS 4.3 yr (95% CI 1.9 – 9.7), followed by Asians 4.0 (95% CI 2.4-5.8), and Whites 2.0 (95% CI 1.4 -2.7) (p-value 0.0125). Among NTC Hispanics had the best OS 1.8 yr (95% CI 1.3 – 2.6), Asians 1.5 (95% CI 1.0 -2.1), and Whites 1.0 (95% CI 0.7 -1.4) (p-value 0.079). Conclusions: Liver transplantation continues to offer the best survival outcomes; however, in a region with long wait times, surgical resection offers a reasonable alternative with favorable survival outcomes. The trend of superior survival amongst Hispanics is noteworthy and subject of further investigation at our center. [Table: see text]
Effect of age on chemotherapy-induced hematologic toxicity
Authors: A. K. Ganti, F. R. Loberiza Jr., A. Kessinger
Journal: Journal of Clinical Oncology (2008)

20634 Background: About 20% of older patients with advanced non-small cell lung cancer (NSCLC) receive chemotherapy. One reason for this is the increased incidence of cytopenias. Limited data exist regarding the effect of age on severity of chemotherapy induced cytopenia. This study was conducted to address this question. Methods: A review was conducted to identify chemotherapy-naïve patients who received standard doses of carboplatin and paclitaxel for NSCLC. Age, gender, smoking and alcohol history and stage at diagnosis were recorded. Values for hemoglobin (Hgb), total white blood cell count (WBC) and platelet (Plt) counts before, and nadir counts following each chemotherapy cycle were obtained. Patients were dichotomized based on age to <60 years old or ≥ 60 years old. Comparisons according to age were performed using Wilcoxon test and Chi-square test (for patient characteristics) while unpaired T-test was used to assess hematological parameters. Multivariate comparisons of change over time of hematological parameters between age groups were performed using mixed models with autoregressive covariance assumption to account for correlated data. Gender, disease stage, smoking and alcohol intake were the co-variates studied. Results: Of the 90 patients identified, 37 (41%) were <60 and 53 (59%) were ≥60 years old. No differences in patient and hematological parameters were noted between age groups. There was no effect of age on either pre-chemotherapy, or nadir values of Hgb, WBC or Plt. Nadir values for Hgb, WBC and Plt correlated with the corresponding pre-chemotherapy values. In the multivariate analysis, pre-chemotherapy and nadir values of the hematological parameters showed a statistically significant decrease over time (chemotherapy cycles) but the decrease was independent of age. Conclusions: Pre-chemotherapy values and number of chemotherapy cycles administered, rather than age affected the nadir counts of Hgb, WBC and plt. Age alone may not be a valid criterion for determining eligibility for chemotherapy in this patient population. Pre-chemotherapy and nadir WBC counts based on age Cycle Pre-chemotherapy Mean (SD) Nadir Mean (SD) WBC count (× 103/μL) Age < 60 yrs Age ≥ 60 yrs Age < 60 yrs Age ≥ 60 yrs 1 9.9 (4.04) 9.40 (3.56) 3.47 (1.57) 3.04 (1.87) 2 7.3 (5.00) 7.00 (2.62) 2.93 (1.69) 2.48 (1.41) 3 5.34 (2.00) 5.73 (2.20) 2.44 (1.54) 2.26 (1.35) 4 5.46 (1.96) 6.04 (2.43) 2.43 (1.00) 2.56 (1.37) 5 4.48 (0.71) 6.61 (3.98) 1.99 (0.72) 2.39 (1.24) No significant financial relationships to disclose.
Study of dynamic contrast-enhanced ultrasound (DCE-US) for the early evaluation in patients included in phase II treated with TKI 258 in renal cell carcinoma.
Authors: B. Benatsou, N. Lassau, F. Tabarout, S. Koscielny, E. Angevin, B. J. Escudier
Journal: Journal of Clinical Oncology (2011)

e13588 Background: To determine the best timing for the early assessment of a functional parameter calculated with DCE-US in order to rapidly distinguish poor responders from good responders among patients treated with TKI 258 in phase II. Methods: All patients had an examination just before the start of TKI 258 (D-1) and at D7, D14, D 30, D 60 and D 120. Each examination included a bolus injection of 4.8 ml of Sonovue (Bracco) and raw linear data were recorded over 3 minutes with an Aplio (Toshiba). The raw linear data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate one parameter (the area under the curve (AUC) correlated with the blood volume) characterizing the tumor perfusion curve. Response to treatment was evaluated with RECIST criteria with scanographic evaluations. Complete or partial responses and stabilization were classified as successes and progression as treatment failure. Results: A total of 7 patients were included for the DCE-US evaluation. According to RECIST criteria, the median time to event of 3 poor responders was 4 months and the time to event of the 4 good responders was always more than 12 months. 36 DCE-US examinations were performed. Among good responders: The median variation in the AUC between baseline and D7, 14, 30, 60 and D 120 was -85%, -55%, -77%, -59% and -81% respectively. Conclusions: Our results confirm the interest of DCE-US for monitoring TKI 258 in metastatic RCC. The dramatic decrease in the AUC started from D7 after the beginning of treatment.
Differential impact of changes in muscle tissue (MT) and adipose tissue (AT) on survival in men and women with locally advanced pancreatic cancer (LAPC) receiving chemoradiation (CRT)
Authors: S. Dalal, D. Hui, L. Bidaut, E. Del Fabbro, C. C. Reyes-Gibby, D. Bedi, K. Lem, K. Hess, C. H. Crane, E. Bruera
Journal: Journal of Clinical Oncology (2008)

9640 Background: Pancreatic cancer carries a high mortality and is frequently associated with cachexia. CT imaging is routine in cancer patients and shown to be accurate for measuring MT and AT. In this study, we aimed to determine the prognostic significance of alterations in MT and AT, and its relationship with weight (wt) loss. Methods: 18 males and 23 females with LAPC participated in a prospective Phase I trial (bevacizumab with concurrent radiotherapy & capecitabine). Abdominal CT images obtained before and after treatment (median 104 days) were analyzed. The average cross-sectional normalized volumes of MT and AT, with the latter made of distinct visceral (VAT) and subcutaneous (SAT) components, from 4 consecutive slices over L3 were obtained. Height, wt, and laboratory data (albumin, hemoglobin, and WBC) were analyzed. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. Results: Median age (59 years, range 42–81) and baseline BMI (26, 95% CI 24–27) was similar in both genders. Males had higher wt (80.7 vs. 63 kg, p < 0.003), MT and VAT (p < 0.0001) but did not differ from females in SAT. Following chemoradiation, males and females had similar median loss in wt, MT, VAT & SAT (5.2, 3, 12, and 11 % respectively, p > 0.5). Wt loss correlated with loss in MT (r =0.67, p 0.002), SAT (0.63, 0.004) and AT (0.75, 0.0004) in males, and with loss in SAT (0.45, 0.03) and AT (0.44, 0.04) in females. Median survival was similar in males & females (240 vs. 282 days, p=0.29). In both genders, wt loss was associated with survival. In males, losses in MT and AT were also significant factors. In multivariate analysis, MT loss in males remained as an independent prognostic factor. Males with >3 % MT loss (N=9) had poorer survival (156 days) than those with ≤ 3 % (N=9, 223 days, p = 0.003), and at baseline had higher BMI and SAT (p <0.02) but did not differ in MT or laboratory data. Conclusions: In LAPC patients, males had higher wt, BMI, MT and VAT than females, and experienced similar losses in wt, MT, SAT and VAT loss during CRT. Our data suggests that MT loss predicts for poorer survival in males but not in females. Future studies of MT and AT measured by CT along with known cachexia mediators and sex hormones are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Genentech
Post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumors: The impact of time
Authors: B. S. Carver, R. J. Motzer, D. Bajorin, J. Stasi, G. J. Bosl, J. Sheinfeld
Journal: Journal of Clinical Oncology (2005)

4581 Background: The integration of chemotherapy and surgery for metastatic non-seminomatous germ cell tumors (NSGCT) results in an overall survival of > 90%. We evaluated NSGCT patients (pts) undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) to assess for associations between year of treatment and clinical outcome. Methods: We evaluated 509 men who underwent PC-RPLND from 1989–2002 for NSGCT at our center. Pts were retrospectively allocated to 3 cohorts according to year of treatment from 1989 to 1992, 1993 to 1997, and 1998 to 2002. Data were obtained from our prospective surgical database and assessed for stage at diagnosis, IGCCCG risk classification, chemotherapy regimen, PC-RPLND histology, and disease free survival. Statistical analysis was performed using SPSS software; p-values < 0.05 were considered significant. Results: From 1989 to 1992, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 3%, 12%, 25% and 54% of patients respectively, compared to 16%, 23%, 17%, and 37%, respectively from 1998 to 2002 (p < 0.001). The prevalence of good, intermediate, and poor risk disease remained similar over time but the need for salvage chemotherapy declined from 21% (1989–1992) to 9% (1998–2002, p = 0.002). Teratoma in the retroperitoneum increased from 34% (1989–1992) to 49% (1998–2002, p = 0.003), while the prevalence of teratoma in the orchiectomy specimen remained similar. The presence of viable NSGCT at the time of PC-RPLND decreased over time. From 1989–1992, 1993–1997, 1998–2002, 19%, 13%, and 6% of patients had persistent viable disease respectively (p = 0.001). Over time, the 5-year actuarial disease free survival has improved (Table). Conclusion: In more recent years men are presenting with less advanced metastatic NSGCT and a smaller percentage require salvage chemotherapy. This stage migration together with effective chemotherapy and surgery has resulted in an improved disease free survival. No significant financial relationships to disclose.
Abstract 18991: Mechanism of False Positive Exercise Electrocardiographic Testing: An Investigation by Advanced Echocardiography
Authors: Masaki Izumo, Kengo Suzuki, Hidekazu Kikuchi, Seisyo Ko, Yu Eguchi, Nobuyuki Azuma, Yoshihiro J Akashi, Kazuto Omiya, Fumihiko Miyake, Takahiro Shiota
Journal: Circulation (2010)

Introduction: Treadmill exercise electrocardiography (TEE) is the classical method for initial assessment of coronary artery disease (CAD). However, a significant number of patients reveal false po...
A phase II trial of induction chemotherapy with cisplatin, docetaxel, and capecitabine followed by concurrent cisplatin-radiotherapy in advanced nasopharyngeal carcinoma.
Authors: M. Yamouni, Y. Beldjilali, K. A. Benhadji, H. Khellafi, F. Betkaoui, Y. Kaid, L. Benchlef, F. Z. Daim, S. Toubal, A. Boukerche, A. Abdelaoui, L. Djellali
Journal: Journal of Clinical Oncology (2011)

5543 Background: The purpose of this study is to assess the antitumor activity and toxicity of a induction chemotherapy regimen combining docetaxel (T), cisplatin (C) and capecitabine (X) followed by concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histologically diagnosed locally advanced nasopharyngeal carcinoma (Stages IVA and IVB, III TNM/UICC 2002) received T 75 mg/m2, P 75 mg/m2 both on day 1 and X 1000 mg/m²/d, days 1-14, with cycles repeated every 3 weeks. All pts received four cycles in a neoadjuvant setting before concurrent C 75 mg/m² day 1, 22, 42 and radiotherapy (4 to 6 weeks after the third cycle of PTX). Pts were evaluated by clinical examination, CT scan of the nasopharynx, the primary end point was tumor response. Results: 89 pts (64 male and 25 female) were enrolled. Median age was 45 years (range 18-67), ECOG performance status was 0-1 in all pts. 68 pts (76%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 21 pts (24%) a poorly differentiated nasopharyngeal carcinoma. 18 pts had stage III disease, 35 pts stage IVA disease and 36 pts stage IVB. Toxicity and tumor response were assessable in 89 pts. After 344 cycles, grade 3-4 toxicities (NCI-CTC 3.0) were: neutropenia (18 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%) and fatigue (10%). No febrile neutropenia was noted. 2 pts had G3 renal toxicity and only one patient had hand-foot syndrome. Response rates for the 89 pts were: complete response 48%, partial response 49% and stable disease 3%. All pts had a complete response after radiotherapy. The disease free survival (DFS) and overall survival at two years was respectively 78 % and 83 %. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. This results need to be confronted with DFS and overall survival after longer follow-up.
Results from SWENOTECA V: A population-based protocol for seminomatous testicular cancer.
Authors: T. Tandstad, R. Småland, O. H. Klepp, E. Cavallin-Stahl, U. Stierner, A. Laurell, P. Flodgren, O. Dahl, G. Cohn-Cedermark
Journal: Journal of Clinical Oncology (2010)

4531 Background: From 2000-2007, 1,380 Norwegian and Swedish patients (pts) with seminomatous germ cell testicular cancer (SGCT) were followed prospectively according to a nationwide community-based treatment protocol, SWENOTECA V. The main objectives were to register all pts within the multicenter setting of the SWENOTECA in order to maintain and possibly improve the good results in the treatment of SGCT. Methods: Staging procedures, treatment and follow-up were standardized according to the protocol. Based upon physician and patient's preference treatment of clinical stage (CS) I pts were between surveillance (n=508) and 25.2 Gy radiotherapy (n=478) given to a para-aortic and ipsilateral iliac field. As data on adjuvant chemotherapy emerged, pts were also offered one course of adjuvant carboplatin (AUC7) (n=185). In clinical stage IIA, recommended treatment was radiotherapy to a total dose of 27.0 Gy. For clinical stages IIB-IV, cisplatinbased chemotherapy in the form of EP × 4 was recommended. However, in highly advanced seminoma initial BEP chemotherapy was recommended. Results: Of all pts 86% were in CS I, 10.7% in CS II, 1.8% in CS III and 1.4% in CS IV. Median follow-up was 4.7 years, IQR 3.2-6.4. OS survival was 97.6% (26 deaths). CSS was 99.6% (6 deaths) with only one death in primary CS I. In CS I surveillance yielded a relapse rate of 15.3%, adjuvant radiotherapy 0.9% and adjuvant Carboplatin 4.2%. In clinical stage IIA, 10.9% (3/29) relapsed after radiotherapy. In comparison no (0/67) CS IIB pts relapsed after chemotherapy. There were no deaths in CS IIA-B. Conclusions: Anationwide community-based treatment protocol for SGCT is feasible with excellent results. Surveillance is a good option for CS I pts. Despite a low relapse rate, adjuvant radiotherapy has now been abandoned in SWENOTECA as a recommended treatment option due to concerns of induction of secondary cancers. Adjuvant carboplatin (AUC7) in CS I will reduce the rate of relapse by about 70% compared to surveillance. The high rate of relapse in CS IIA pts treated with radiotherapy is of concern, especially when compared to the low number of relapses in CS IIB pts treated with chemotherapy (p=0.011). No significant financial relationships to disclose.
A pharmacokinetic (PK) study of AC480 administered twice daily in patients with surgically resectable, recurrent malignant glioma (MG) not on enzyme-inducing antiepileptic drug (EIAED).
Authors: A. Desjardins, D. A. Reardon, J. J. Vredenburgh, K. Peters, M. Trikha, J. James, M. Gardner, A. Brickhouse, J. E. Herndon, H. S. Friedman
Journal: Journal of Clinical Oncology (2011)

2070 Background: AC480 is a novel oral tyrosine kinase inhibitor of the human epidermal growth factor receptor family, especially EGFR and HER2. EGFR is an important therapeutic target in MG. We performed a pilot study to evaluate the tumor and plasma PK of AC480 among patients with recurrent MG. Methods: Eligibility included: adult patients with < three recurrences of a WHO grade 3 or 4 MG; candidate to surgical resection; prior treatment with radiotherapy and chemotherapy; Karnofsky >60%; adequate hematologic, renal and liver function. Exclusion included use of EIAED and prior targeted therapies to EGFR and HER2. FDG-PET was obtained at baseline, then AC480 was initiated at 300 mg orally BID. FDG-PET was repeated on day 14. Patients remained on treatment until surgery (day16). Plasma PK were obtained on days 1, 14 and 16. Tumor specimen for tumor PK was obtained at surgery. Patients resumed AC480 7 to 21 days post-surgery. Results: As planned, 5 patients were enrolled on study (WHO grade 4, n=4; WHO grade 3, n=1). Median age was 58 (range, 36-65). All patients completed FDG-PET and surgery. Three patients had same or decreased metabolic activity on day 14 FDG-PET; two had increased metabolic activity. Following surgery, 4 patients resumed therapy, one patient refused, as pathology showed WHO grade 2. One patient remains on therapy after 45+ weeks. Two patients progressed 4 weeks after resuming AC480 and one after 8 weeks. One patient each experienced grade 3 proteinuria and leukopenia. Tumor PK levels were variable, but AC480 was present in all samples. Concentrations ranged from 2561 to 8703 ng/mL (5 to 16 uM). Tumor/Plasma PK ratios ranged from 3 to 11, indicating tumor levels exceeded plasma levels in all patients. Conclusions: AC480 is well tolerated and reaches the brain with tumor PK levels exceeding plasma. Further trials combining AC480 with chemotherapy or other targeted therapies are warranted.
Interferon alpha + 13-cis-retinoic acid modulation of BCL-2 + paclitaxel for recurrent SCLC
Authors: J. Aisner, S. Dahlberg, J. S. Rodgers, S. C. Aisner, J. H. Schiller
Journal: Journal of Clinical Oncology (2008)

19048 Background: While SCLC is highly responsive to initial chemotherapy, second line therapy is more challenging, since most cases develop resistance to chemotherapy after first line therapy. SCLC is known to over-express bcl-2, and such over-expression can produce drug resistance by inhibiting apoptosis. The combination of CRA and IA was shown to reduce bcl-2 expression, and potentially enhance drug sensitivity to several agents such as taxanes. Methods: The primary endpoints were to evaluate objective response rate (ORR) defined per RECIST and toxicities in patients (pts) with SCLC recurrent > 60 days from prior chemotherapy and who were then treated with IA, and CRA modulation of bcl-2 plus P. Secondary endpoints include progression-free survival (PFS) and overall survival (OS). Eligibility criteria included: ECOG PS 0–3, and adequate hematological, hepatic, and renal function. Pts received IA 6 million U/m2 SQ, on days 1 and 2, CRA 1 mg/kg PO on days 1 and 2 and P 75 mg/m2 IV on day 2 each week for 6 weeks then 2 weeks of rest. The study employed a two-stage design with 34 pts entered in the first stage (FS). If more than 12 ORRs were observed, then 42 more pts would be entered. If more than 31 ORRs were observed in 76 pts, then the treatment would be regarded as efficacious. Results: From 2/04 - 2/07, 37 pts were registered to the FS of this study. Two were ineligible. All pts had measurable disease, 5 pts (14%) had pleural effusion. At the end of the FS 3 ORRs (10.3%, 90% CI = 2.9%, 24.6%), all PRs, had been observed in 29 pts with sufficient data to evaluate ORR. Median follow-up is 14.7mos; median OS is 6.4 mos (3.9–9.7 mos); median PFS is 2.3 mos (1.8–4.6 mos). 21 pts (62%) experienced worst degree toxicity of grade 3 or higher; the most common of which were leukocytes (32%) and neutrophils (26%). Conclusion: This study was terminated for not meeting the criteria to reopen the second stage of the study. The response and survival data seen were no better than P alone. IA plus CRA plus P did not provide a sufficient clinical benefit for pts with recurrent SCLC to warrant further study of this combination, however analysis of peripheral blood monocytes’ bcl-2 protein is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Pfizer, Roche
Adjuvant chemotherapy for stage II colon cancer: Who (really) needs it?
Authors: N. F. Esnaola, P. Mauldin, M. Ebeling, T. Hulsey, B. Liu, M. B. Thomas, Y. Yang
Journal: Journal of Clinical Oncology (2011)

e14150 Background: Despite data suggesting that failure to meet a benchmark of 12-13 lymph nodes in resection specimens is associated with worse prognosis in patients with stage II colon cancer and may be an indication for adjuvant therapy, its use in this setting remains controversial. The objective of this study was to determine the benefit of chemotherapy in patients with stage II colon cancer according to the number of lymph nodes examined. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 9,651 patients aged 66 and older with resected stage II colon cancer diagnosed between 1999-2004. Use of chemotherapy within 3 months of surgery was ascertained from Medicare claims. The relationships between patient/tumor characteristics (including number of lymph nodes examined) and use of adjuvant chemotherapy were analyzed using chi square tests and logistic regression. Survival for treated and untreated patients was compared using multivariate Cox models. Results: The majority (54.8%) of patients had only 1-12 nodes examined, while only 41.6% of had >12 nodes examined. Overall, 20.9% of patients received adjuvant chemotherapy; there was no association between number of lymph nodes examined and chemotherapy use (P=0.984). Presence of 12 or less nodes in the surgical specimen was associated with worse overall survival (adjusted hazard ration [HR] 1.31, 95% confidence internal [CI] 1.21 to 1.41). Although adjuvant chemotherapy was associated with improved outcomes in our cohort, its beneficial effect on disease-free survival (adjusted HR, 0.73; 95% CI, 0.62 to 0.83) and overall survival (adjusted HR, 0.71; 95% CI, 0.59 to 0.85) was limited solely to patients with 0-12 nodes examined. Conclusions: Retrieval of 12 or fewer nodes in surgical specimens is associated with worse prognosis and survival benefit with use of adjuvant chemotherapy in patients with stage II colon cancer. A greater emphasis on achieving recommended benchmarks for lymph node dissection is needed to help identify patients who may truly benefit from adjuvant chemotherapy after colectomy.