tbuckley/cabot-search huggingface dataset:
Adjuvant chemotherapy and overall survival in patients with node positive esophageal adenocarcinoma treated with neoadjuvant therapy and esophagectomy: A retrospective analysis using the National Cancer Database.
Authors: Gaurav Ajmani, Thomas A. Hensing, Ki-Wan Kim, Seth B. Krantz, Richard A Prinz, Mark S. Talamonti, Marshall Baker, David J. Bentrem, Kevin K. Roggin, Robert de Wilton Marsh
Journal: Journal of Clinical Oncology (2017)

97 Background: Node positive disease (N+) is frequent (~40%) following neoadjuvant therapy (NAT) and esophagectomy, yet limited data exist regarding the efficacy of adjuvant chemotherapy (AC) in this setting. There are no randomized studies addressing this question and single-institution, retrospective studies have reported mixed findings. Methods: A retrospective analysis was conducted using the National Cancer Database. 2,258 N+ patients were identified who had received NAT (83.3% chemoradiation and 17.7% chemotherapy alone) followed by esophagectomy. Patients with either incomplete staging or treatment data were excluded, as were those who died within 90 days following esophagectomy. Multivariate logistic regression was used to test for differences in patient characteristics between those who did (AC+) or did not (AC-) receive AC. Overall survival (OS) after surgery, by AC status, was analyzed using Cox regression in a sample propensity matched on relevant demographic and clinical factors. Results: 433/2258 patients received AC (19.2%). Patients who received AC tended to be younger (OR 0.98 per 1-year increase, P = .03) and had a higher socioeconomic status (SES) (OR 1.47 for high vs. low SES, P = .01). Although there were no significant differences in comorbidity (P = .32), AC+ patients had significantly shorter hospital stays after surgery (OR 0.98 per 1-day increase, P = .03). Pathologic T classification was unrelated to the likelihood of receiving AC (P = .39), however patients with a higher pathologic N stage were more likely receive AC (OR 2.12 for pN3 vs. pN1, P &lt; .001). Those receiving AC had demonstrably longer OS from the time of surgery than those who did not (HR 0.78, P = .004). Median OS for the entire cohort was 22.6 months, whereas the administration of AC was associated with an improvement in median OS of 6.2 months (26.3 vs. 20.1 months). Conclusions: This retrospective analysis indicates that AC is associated with a significant improvement in OS (median 6.2 months) in N+ patients following NAT and esophagectomy. Further studies are needed to clarify the optimal role of AC in this setting.
IMAAGEN trial update: Effect of abiraterone acetate and low dose prednisone on PSA and radiographic disease progression in patients with non-metastatic castration-resistant prostate cancer.
Authors: Charles J. Ryan, E David Crawford, Neal D. Shore, Willie Underwood, Anil Londhe, Shawn C. Black, Tracy McGowan, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2015)

5053 Background: Abiraterone acetate (AA) 1000mg, in combination with prednisone (P), 10mg daily is indicated for the treatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). IMAAGEN is a phase II, multi-center study with a primary endpoint that evaluated the ability of AA plus 5 mg of prednisone (AA+5) to decrease PSA levels in pts with nmCRPC and a rising PSA; primary results have been reported earlier1. Herein we report updated results on secondary endpoints and safety from the IMAAGEN study (Nov 3, 2014 database cut-off date). Methods: All enrolled pts had high risk non-metastatic castration resistant prostate cancer (nmCRPC): PSA value ≥ 10ng/mL or PSA doubling time ≤ 10 months at screening. Pts received AA+5 daily; each treatment cycle = 28 days. Reported endpoints include time to PSA progression, time to radiographic progressive disease, and safety. Results: At the time of the data cutoff, 62 (47.3%) of the 131 patients enrolled in IMAAGEN remained on treatment in the study. The median duration of exposure was 17.9 months (range 0.1 – 40.7 months). Median time to PSA progression was 28.7 months (95% CI 21.2, NE). There were 21 confirmed radiographic progression events. The median time to radiographic progressive disease was not reached. 95.4% of pts had an adverse event (AE) (54.9% had a Grade 3 or higher) and 38.2% had a serious AE (SAE) with 35.9% having an SAE of Grade 3 or higher. 13.0% of pts had AEs resulting in discontinuation of study treatment. Four pts had AEs resulting in death (coronary artery disease, myocardial infarction, acute respiratory failure, and pneumonia). Conclusions: Treatment of high risk nmCRPC patients with AA+5 resulted in a median time to PSA progression of 28.7 months. The median time to radiographic disease progression was not reached. The safety profile of AA+5 reported in this IMAAGEN trial update is consistent with the safety profile from previously reported studies of abiraterone acetate 1000mg in combination with either 5mg or 10mg prednisone. 1ASCO 2014 IMAAGEN primary endpoint poster presentation Clinical trial information: NCT 01314118.
Medications for urologic malignancies in the open payments data: Financial relationships between industry and urologists.
Authors: Mahir Maruf, Abhinav Sidana, Stephanie Purnell, William Fleischman, Sam Joseph Brancato, Shantanu Agrawal, Piyush K. Agarwal
Journal: Journal of Clinical Oncology (2017)

74 Background: The Open Payments program was enacted to increase transparency of the financial relationships between physicians and the pharmaceutical industry. We examined the non-research related financial relationships between urologists and industry in the US using the 2014 Open Payments data as it pertains to payments associated with drugs used in the treatment of urologic cancers. Methods: A descriptive analysis of the Open Payments data released by the Centers for Medicare &amp; Medicaid Services for 2014 was performed. The total payment amount associated with medications prescribed by urologists to treat urologic malignancies was calculated. Results: For drugs associated with all urologic cancers, 44,200 payments, totaling $4,693,561, were made to 5666 urologists. Approximately 82% of payments (76% of the financial value) associated with urologic cancers were for prostate cancer. Of these, payments were primarily associated with anti-androgen therapy ($2,803,435, 79%), followed by hormonal therapy ($672,342, 19%) and chemotherapy ($63,693, 2%). Payments were most commonly in the form of food and beverage (90%), but were only 18% (0.8M) of the total payment amount. Janssen Scientific Affairs reported the largest proportional value of financial ties (24% or 1.1M) but this only accounted for 3% of the number of payments. Conclusions: Nearly 66% of urologists have received a non-research related payment associated with a urologic cancer drug from industry in 2014. Payments associated with prostate cancer drugs were largest in sum and frequency, and consisted largely of payments associated with anti-androgen therapy. This likely coincides with the fact that urologists predominantly prescribe anti-androgens and the recent FDA approval of newer anti-androgens within the last decade.
Updated results from a phase III trial of sunitinib versus placebo in patients with progressive, unresectable, well-differentiated pancreatic neuroendocrine tumor (NET).
Authors: Aaron Vinik, Eric Van Cutsem, Patricia Niccoli, Jean-Luc Raoul, Yung-Jue Bang, Ivan Borbath, Juan W. Valle, Peter Metrakos, Denis Smith, Jen-Shi Chen, Dieter Hoersch, Daniel E. Castellano, Hagen F. Kennecke, Joel Picus, Guy Van Hazel, Shem Patyna, Dongrui (Ray) Lu, Richard C. Chao, Eric Raymond
Journal: Journal of Clinical Oncology (2012)

4118 Background: In a double-blind phase III trial, sunitinib (Sutent; SU) improved progression-free survival (PFS) vs placebo (PBO; 11.4 vs 5.5 mos; HR: 0.42, 95% CI: 0.26–0.66; P=0.0001) and was well tolerated in patients (pts) with unresectable, well-differentiated pancreatic NET that had progressed ≤12 mos before baseline. Initial overall survival (OS) revealed a benefit for SU vs PBO, although median OS had not been reached. We now report PFS assessed by blinded independent central review (BICR) and updated OS. Methods: Pts were randomized 1:1 to SU 37.5 mg or PBO on a continuous daily dosing schedule, each with best supportive care. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint to be evaluated every 2 yrs for 5 yrs, or until 95% of pts had died. Additionally, BICR was performed retrospectively; baseline and on-study CT/MRI scans were evaluated by a 2-reader, 2-time-point lock, followed by a sequential locked-read, batch-mode paradigm by blinded, third-party radiologists. Results: 171 pts were randomized (SU, n=86; PBO, n=85) from Jun 2007 to Apr 2009. The trial ended when an independent data monitoring committee noted efficacy favoring SU and more serious AEs and deaths with PBO. The study was unblinded at closure; pts were offered open-label SU and followed for survival. Median PFS by BICR was 12.6 mos (SU) vs 5.8 mos (PBO) (HR: 0.32, 95% CI: 0.18–0.55; P=0.00001). At study closure, there were 9 and 21 deaths in the SU and PBO arms (HR: 0.41, 95% CI: 0.19–0.89; P=0.02). By Apr 2011 (2 yrs additional follow-up) a total of 87 deaths occurred (51%), median OS was estimated at 33.0 mos in the SU arm, and 26.7 mos in the PBO arm (HR: 0.71, 95% CI: 0.47–1.09; P=0.11 [Table]). 69% of pts crossed over to SU on progression. Conclusions: BICR confirmed investigator assessment of PFS and demonstrated a 6.8-mo improvement in median PFS with SU. Updated OS favors SU, although this result is non-significant for reasons that may include crossover of treatment and limited statistical power. [Table: see text]
Impact of ATG on new HLA groups for unrelated donor allogeneic stem cell transplantation.
Authors: Soo Jung Lee, Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, Joon Ho Moon, Sang Kyun Sohn, Jin Ho Baek, Yoon Young Cho, Yoo Jin Lee, Jun Young Choi
Journal: Journal of Clinical Oncology (2012)

6536 Background: The outcomes of unrelated donor transplantation have improved with refinements in HLA testing. Recently, grouping of HLA matching for unrelated donor was suggested, defining by well-matched, partially-matched, and mismatched. In the current study, the role of ATG for each group was evaluated. Methods: A total of 92 patients diagnosed as hematologic diseases and received allogeneic stem cell transplantation (SCT) from unrelated donor were retrospectively analyzed. Results: Nineteen patients were classified as well-matched, 42 as partially-matched, and 31 as mismatched. Among them, 57 patients received anti-thymocyte globulin (ATG) as graft-versus-host disease (GVHD) prophylaxis. The overall survival (OS) rate was higher for well-matched group (83%) compared to partially-matched (54%) and mismatched (34%, p=0.076). For partially-matched group, the OS was significantly improved with ATG (83.3% vs. 38.6%, p=0.018). But, the OS was not different between groups with or without ATG for well-matched (87.5% vs. 66.7%, p=0.487) and mismatched (32.4% vs. 41.7%, p=0.215). ATG decreased the cumulative incidence of grade 3-4 acute GVHD (10% vs. 40.2%, p=0.068) and severe chronic GVHD (21.2% vs. 52.2%, p=0.037). The use of ATG (HR=0.248, p=0.029) was related with favorable OS for partially-matched group. However, the favorable effect of ATG was not observed in well-matched and mismatched groups. Conclusions: ATG effectively improved survival rate for partially-matched group in unrelated donor transplantation. However, the positive effect of ATG was not observed in well-matched and mismatched group.
Phase II trial of anti-transforming growth factor-beta (TGFß) monoclonal antibody GC1008 in relapsed malignant pleural mesothelioma (MPM).
Authors: James Stevenson, Hedy Lee Kindler, Daniel Schwed, Anjana Ranganathan, Mona Jacobs-Small, Jennfier Shouldis, Amy Marshall, Daniel Heitjan, Corey J. Langer, Frank James Hsu, Steven Albelda
Journal: Journal of Clinical Oncology (2012)

7077 Background: TGFβ is a pleiotropic cytokine overexpressed by MPM. Based on preclinical data documenting a key role for TGFβ in promoting growth and progression of MPM, we are conducting a phase II trial of GC1008 in patients (pts) with progressive MPM. Methods: Pts with progressive MPM by modified RECIST criteria and PS 0-1 with 1-2 prior systemic therapies (at least 1 pemetrexed-based) are eligible. Treatment plan: GC1008 3mg/kg IV over 90 minutes every 21 days. Responses are assessed by modified RECIST every 6 weeks. The primary endpoint is progression-free survival (PFS) rate at 3 months; secondary objectives include safety with GC1008, response rate by modified RECIST, time to progression (TTP), and overall survival (OS). Results: The modified Gehan stage 1 stopping criterion of 1/13 pts with 3 month PFS has been exceeded. To date, 13 pts (10 PS 0; 3 PS 1) with MPM (median age 69; 2F, 11M; 11 epithelial, 1 sarcomatoid, 1 biphasic) enrolled. Treatment-related toxicities include G1/2 fatigue (3 pts), nausea (1 pt) and xerosis (1 pt). Other adverse events possibly related to GC1008 were rapid disease progression in 1 pt after 2 cycles, and G2 skin keratoacanthoma in 1 pt after 5 cycles. Three pts met the primary objective of 3 month PFS at 4.1, 4.2 and 9 months each. Stable disease (SD) was seen in 3 pts (23%). Median TTP is 1.4 months (95% CI 1.2-∞); median OS is 13 months (95% CI 6-∞). Increased serum mesothelin levels have closely tracked disease progression. Serum from 6/13 pts showed new antibodies against MPM tumor lysates as measured by immunoblotting. Two of 3 pts with SD had anti-tumor antibody responses. Mean baseline plasma level of TGFβ was 2447 pg/ml but did not correlate with baseline plasma TGFβ or TTP. Conclusions: GC1008 was well tolerated in pretreated MPM patients. SD occurred in 3 pts, all with prior disease progression. Evidence for humoral anti-tumor immunity was seen in nearly half of enrollees and in 2 of 3 pts with SD. OS compares favorably to prior single-agent studies in pretreated MPM.
Olfaction as a soldier-- a review of the physiology and its present and future use in the military
Authors: Palaniappan Ganesh Nagappan, Somasundram Subramaniam, De-Yun Wang
Journal: Military Medical Research (2017)

Olfaction is one of our 5 main qualitative sensory abilities. In this review, we have examined the physiology of olfaction from the olfactory receptor to the brain. Through analyzing the physiology of olfaction, we have found that the biochemistry of olfactory nerve stimulation is unique from that of other similar pathways. Upon receiving large amounts of input from the olfactory nerve, the olfactory bulb, followed by several layers of centrifugal and centripetal processing in the brain, has to sort the information from the input as well as integrate it with other inputs from the brain to develop a coherent understanding of the input. We then examined the implications of olfaction in the military, the practical applications of electronic noses and problems associated with injury to olfaction that could affect compensation and combat worthiness of a soldier following injury. In the military, olfaction can allow the army to perform at its best through 4 main methods, namely ensuring olfaction is consistent with other dimensions of perception (ensuring optimal olfaction ability in all soldiers in combat), understanding the impact of different common combat environments on the sense of smell, utilizing odor as a defense mechanism and using olfactory aids when necessary. Electronic noses are olfactory aids that have a large potential in the military ranging from saving lives through the detection of explosives to potential methods for improving combustion efficiency. There are several problems associated with injury to olfaction that should be considered when deciding on compensation and combat worthiness of the soldier following an injury.
Phase II study of S-1 in combination with paclitaxel as a first-line treatment for patients with advanced/recurrent gastric cancer
Authors: U. Toh, H. Yamana, K. Koufuji, T. Mine, K. Aoyagi, M. Miyagi, T. Imaizumi, K. Shirouzu
Journal: Journal of Clinical Oncology (2009)

e15615 Background: Taxanes and S-1 have been shown to be effective in patients with advanced gastric cancer and they have a considerable single-agent activity, respectively. We evaluated the combination of paclitaxel and S-1 as first-line chemotherapy for advanced or recurrent gastric cancer (AGC). Methods: All patients with histologically confirmed AGC with unresectable or metastatic diseases, measurable lesions, PS 0–2, age between 18 and 75, and no contraindication to chemotherapy were eligible in this study. Prior adjuvant chemotherapy finished at least 6 months before enrollment was allowed. Treatment included S-1 80 mg/m 2 p.o. twice daily on days 1–14 and paclitaxel 60 mg/m 2 i.v. on day 1, 8, 15 with a 2-week interval until disease progression or unacceptable toxicities. Results: Between MAY 2004 and Match 2008, total 20 pts were enrolled in this study. The median age was 56.5 years (range, 38–73). Nine pts had recurrent disease after previous curative gastrectomy and 8 had previous adjuvant chemotherapy. After a median 4 (range, 1–9) cycles of chemotherapy, 12 pts were evaluable for toxicity and 20 pts for response. In intention-to-treat analysis, the overall response rate was 62.9% (95% C.I., 36.2–69.6%), including 0 CR, 6 PRs, 8 SDs, and 6 PDs. After a median follow-up of 8.6 months (range, 0.9–17.9), median time to progression was 6.3 months (95% C.I., 3.6–6.9) and median overall survival was 11.6 months (95% C.I., 8.5–20.7). Commonly observed grade 3/4 adverse events were neutropenia (40% of patients), anemia (10%). There was no neutropenic fever or treatment-related death. Conclusions: The combination of paclitaxel and S-1 appear to have well efficacy, manageable toxicity and is well tolerated in patients with AGC. Further studies of this combination should be considered. No significant financial relationships to disclose.
Developmental pharmacokinetics of topotecan (TPT), a renally excreted drug, in infants and young children with brain tumors.
Authors: Vinay M. Daryani, Katheryn Elaine Harstead, Jeffrey F Scott, Deborah A Ward, Stacy L Throm, Daniel C. Bowers, Anne Elizabeth Bendel, Paul Graham Fisher, Karen D. Wright, Alberto Broniscer, Giles W. Robinson, Amar J. Gajjar, Clinton F. Stewart
Journal: Journal of Clinical Oncology (2015)

10055 Background: We investigated TPT pharmacokinetics (PK) in a clinical trial evaluating risk adapted therapy for infants and young children with brain tumors (NCT00602667). During consolidation, TPT is administered over 4 hrs to high risk patients on days 1 – 5; the initial dosage is based on age (patients < 6, 6 – 11.9, and > 12 months receive 2, 2.5, and 3.5 mg/m2, respectively). Methods: PK studies are performed using a limited sampling strategy (time points: pre-infusion, 5 mins, 1, and 3 hours post infusion). TPT lactone concentrations are measured by HPLC-UV using a CLIA-approved assay. We use a PK-guided approach to individualize the TPT dosage to achieve a daily target plasma AUC0-∞ of 120 – 160 ng/mL*h. In this report we analyzed the individual TPT data from 38 patients using a population PK approach. A two-compartment PK model was fit to the TPT concentration-time data using nonlinear mixed effects modeling to estimate population PK parameters and inter- and intra-subject variability. Estimated PK parameters included volume of the central compartment (Vc), total systemic clearance (Clt), and intercompartmental rate constants (Kcp, Kpc). Results: In the 38 patients, we collected and analyzed 396 samples. The median (range) age, body surface area (BSA), and actual weight are 22.6 months (6 – 42 months), 0.54 m2 (0.31 – 0.69 m2), and 12 kg (5.4 – 16.9 kg), respectively. The population mean (RSE%) estimates of plasma TPT lactone Clt and Vc were 25.7 (4.8) L/h/m2 and 24.2 (5.8) L/m2, respectively, with interindividual variability (%CV) of 24% for Clt and 22% for Vc. The median (range) TPT Clt in 9 patients < 12 months old was 20.6 L/h/m2 (10.8 – 29.9 L/h/m2) and was significantly lower (Mann-Whitney p < 0.0001) compared to 29 patients ≥ 12 months old with a median (range) TPT Clt of 28.3 L/h/m2 (16.7 – 45.1 L/h/m2). Conclusions: TPT Clt exhibits an age-dependency independent of BSA and the increase in TPT Clt parallels the physiological maturation in renal function that occurs during infancy. These results validate our use of lower initial TPT dosages in infants and point to incorporation of a maturation function on clearance to further refine our dosing approach for TPT in infants and young children with brain tumors. Clinical trial information: NCT00602667.
AIDS-related lymphoma (ARL) in Asians in the era of HAART and rituximab.
Authors: Wu Meng Tan, Soo Yong Tan, Tat Ming Ng, Summer Pan, Richard Hong Hui Quek, Miriam Tao, Wai Meng David Tai, Yin Ling Koh, Thuan Tong Tan, Daryl C.L. Tan, Tam Cam Ha, Alexandre Chan, Kevin Tay, Soon Thye Lim
Journal: Journal of Clinical Oncology (2012)

e18546 Background: We described EBV &amp; HHV8 co-infection rates, histology subtypes (particularly T-cell), prognosticators and outcomes of Asian ARL and compared them to Western series. Methods: We studied clinicopathologic features of 46 HAART-era ARL diagnosed from 1998-2011 in an Asian Tertiary Cancer Centre. To study HIV effect on survival, we applied multivariate analysis to HIV-DLBCL matched against 453 de novo DLBCL from 2000-2008. Results: The 46 patients’ characteristics are presented in the table below. Of note, germinal centre B-cell (GCB) subtype predominated in HIV-DLBCL with evaluable tissue. In multivariate analysis of HIV-DLBCL and matched de novo DLBCL, HIV status did not predict survival (HR1.33, p=0.63); CR was the only significant prognosticator (HR0.30, p=0.048). Conclusions: 1. EBV+ rates appeared to surpass prior Western ARL series. Although concomitant EBV infection appeared to correlate with inferior survival (HR34.5), it was not statistically significant. 2. Alb&lt;30 (p=0.02) &amp; Hb&lt;10 (p=0.003) significantly predicted worse OS, but not CD4 or concurrent HIV&amp;ARL diagnosis. 3. In this predominantly EPOCH-treated population, BL (HR 2.27) non-significantly trended to worse OS than DLBCL. 4. T-cell ARL (2/46, 4%) was rarer than the expected Asian de novo rate. 5. In multivariate analysis, HIV-DLBCL OS was similar to matched de novo DLBCL, suggesting they should be similarly treated with curative intent. CR rates and 5yr OS were comparable to de novo DLBCL. [Table: see text]