tbuckley/cabot-search huggingface dataset:
A phase II study of the combination of liposomal doxorubicin (LD) and gemcitabine (G) in patients with relapsed ovarian cancer after chemotherapy containing platinum compounds
Authors: A. Gambino, G. Tognon, G. Galleri, L. Agoni, S. Pecorelli
Journal: Journal of Clinical Oncology (2005)

5154 Background: Treatment of choice for patients (pts) with platinum-resistant ovarian cancer (OC) is to be defined. LD is active in relapsed OC with a response rate of 25%. G has shown activity as second line chemotherapy. Our purpose was to evaluate the activity and safety of the LD and G combination chemotherapy in relapsed OC pts, previously treated with at least one platinum containing regimens. Methods: Between Apr 2002 and November 2004, 20 pts with recurrence of histologically proven epithelial OC entered the study and were treated with G 700 mg/m2 (30 min i.v.) on day 1,8 and LD 30 mg/m2 (120 min i.v.) on day 1, every 28 days. The study is still ongoing, so 5 pts are not yet evaluable for response. Results: Characteristics of the pts were the following: median age of 56 years (range 31–74); ECOG PS 0; histology: serous 12 pts, clear cell 3 pts, endometrioid 2 pts, poorly differentiated 2 pts, mucinous 1 pt, mucinous borderline 1pt; initial FIGO stage: III in 16 pts, II in 2 pts, IC in 1 pt, IV in 1 pt. All pts were pretreated with at least one platinum containing chemotherapy. Toxicity consisted of: grade 3–4 (NCI-CTC) neutropenia in 60% of pts, palmo-plantar erythrodysesthesia (PPE) in 40% of pts (grade 1 in 30% of pts, grade 2 in 10%), mucositis in 15% of pts. Doses of LD were reduced by 10–25% in 3 pts due to haematological toxicity or PPE. Filgrastim was administered in 7 pts with neutropenia and EPO was administered in 1 pt with anemia. No neutropenic fever nor unespected toxicity or treatment-related deaths were observed. A total of 145 cycles were administered, with a median of 7 cycles for pt (range 2–14). Objective responses were observed in 40% of pts (6/15 pts) after 2 to 7 cycles (median 3): 4 pts had complete response, 2 pts had partial response. The mean duration of response was 21.3 weeks (range 8–44). The other 9 pts had a stable disease for a mean duration of 25.7 weeks (range 4–52). The mean progression free survival for all pts was 22.9 months (range 4–52). At follow up 7 pts were AWD, 8 were DOD. Conclusions: In this patient population the LD and G combination, with schedule and doses described, is active, with mild and manageable toxicity. No significant financial relationships to disclose.
A randomized single blind controlled trial of beads versus doxorubicin-eluting beads for arterial embolization of hepatocellular carcinoma (HCC).
Authors: Karen T. Brown, Mithat Gonen, Kinh Gian Do, Anne M. Covey, George I. Getrajdman, Binsheng Zhao, Constantinos T. Sofocleous, Kristian Johnson, Christopher Beattie, Ronald P. DeMatteo, Stephen Barnett Solomon, Lawrence H. Schwartz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2013)

143 Background: HAE using particles is a method of treatment for HCC. The added role of doxorubicin has never been fully understood biologically. To date, no study has demonstrated any difference in outcome using HAE versus trans-arterial chemoembolization (TACE). Methods: Patients (pts) with unresectable Okuda stage I or II HCC with adequate liver function were randomized to BB or LC loaded with 150 mg of doxorubicin. Pts were evaluated by multiphasic CT 2-3 weeks post-treatment. Progression by RECIST and/or evidence of ≤5% necrosis was considered treatment failure. Otherwise pts were followed with CT every 3 months until progression or death. Pts with either recurrent tumor or new tumor outside the treated area could be re-treated. The primary objective was response rate (RR) by RECIST. With 50 pts in each arm response rates can be estimated to within +/- 14%. Secondary objectives included assessing safety and tolerability, time to progression (TTP), progression free survival (PFS), and overall survival (OS). Quantification of tumor necrosis (TN) using CT volumetric data was correlated with outcome. Analyses were intention-to-treat. Results: Between December of 2007 and March of 2012, 101 pts were randomized, 51 to BB and 50 to LC. Demographics in the two groups were comparable: median age was 67, 77% were male and 81% were Okuda I. Median number of embolizations was 2 in both arms. There was no difference in adverse events, the most common being post-embolization syndrome of pain, fever, nausea, or vomiting (84% in both groups). There was no difference in RR: BB 11% vs LC 9% (p=0.58). Median TTP was not reached. 12 month TTP was 49 versus 56% (p=0.84), median PFS was 7 versus 9 (p=0.6), and OS 14 versus 16 months (p=0.7) for BB and LC respectively. Change in TN/tumor volume post treatment did not predict OS in either group (p=0.28). Conclusions: No difference in response was noted between pts treated with BB versus LC. Given the comparable safety profile, TTP, PFS and OS, HAE should be considered a reasonable and cost-effective therapeutic option and may be preferable to LC. Clinical trial information: NCT00539643.
Improving infusion therapy efficiency at the Woodlands Regional Care Center (RCC).
Authors: Jeremy Meade
Journal: Journal of Clinical Oncology (2012)

84 Background: The Woodlands RCC opened the Ambulatory Treatment Center in September 2010. The center houses 14 infusion units. Within 1 year, the demand for its infusion therapy services had more than doubled with continued rapid growth expected. The perception was that more patients could not be accommodated without additional space and staff. Therefore, a performance improvement team was formed in August 2011 with the goal to increase operational efficiency to satisfy patient demand, while maintaining the highest level of quality care. The increased access for patients allows for treatment to start sooner. Methods: The six sigma Define-Measure-Analyze-Improve-Control methodology was used to manage the project, and several lean and six sigma tools were utilized. The project commenced with a project charter with a measureable AIM statement to increase infusion volumes from 1.7 to 2.4 patients/unit per 9 hour day. Historical data was extracted, and all patients’ movements were timed for 3 weeks. Benchmarking, observations, and process mapping were also performed. Baseline performance was measured using SPC charts. Sources of variation were uncovered using statistical quality tools, brainstorming techniques, and cause/effect analysis. Key interventions consisted of standardized scheduling practices, development of a scheduling template, creation of a fast track room, new processes for overbooks and preschedules, and work balancing of nursing staff using an acuity rating system. In addition, staff workload was redistributed, and the lab was reorganized. Results: Within 3 months, the center met targeted capacity and provided regional care access to 41% more patients without additional staff, space, or working hours. By March 2012, the center accommodated 67% more patients (2.9/unit or 40/day) without adversely affecting patient wait time. Infusion room utilization increased by 15%. Conclusions: Although space constrained, The Woodlands RCC was presented with the challenge to provide patients’ open access to infusion therapy services. The team successfully applied lean and six sigma principles to evaluate the current state, perform a gap analysis, and deploy interventions to support quality and operate more efficiently.
Proteinases in testicular germ cell tumors
Authors: F. E. v. Eyben, R. I. Skotheim, G. K. Jacobsen
Journal: Journal of Clinical Oncology (2005)

4773 Background: Proteinases play a role for invasiveness of malignancy so we examined data from a previous DNA oligo microarray study of patients with testicular germ cell tumors (TGCT). Methods: The study included 3 normal testis, 3 intratubular germ cell neoplasias (IGCN), 3 seminomas (S), 5 embryonal carcinoma (EC), 1 choriocarcinoma, 4 yolk sac tumors, and 4 teratomas (TER). From the DNA microarray data set, we selected the mRNA expression of matrix metalloproteinases (MMP), plasminogen activator, urokinase (PLAU), and plasminogen activator inhibitor 1 (PAI-1, SERINE1), and compared gene expressions for histological groups of testicular cancer using nonparametric statistics. Results: A series of statistically significant differences were identified between histological groups of testicular cancer: between IGCN and TGCT (MMP9, MMP12, PLAU, and SERINE1), between S versus IGCN and non-S (MMP2 and MMP19), between S and non-S (MMP11), and between TER and non-TER (MMP7 and MMP17). Conclusions: Several MMPs, PLAU, and SERINE1 contribute to invasiveness, and histological subtypes of TGCT have separate characteristic patterns of expression of these proteinase genes. No significant financial relationships to disclose.
Improving quality of care within the NCI Community Cancer Centers Program (NCCCP) network.
Authors: Kathleen M. Castro, Eliot Lawrence Friedman, Nadesa Mack, Robert D. Siegel, Jana Eisenstein, Irene Prabhu Das, Steven Clauser
Journal: Journal of Clinical Oncology (2013)

178 Background: The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) was initiated to expand cancer research and deliver quality cancer care in communities. A program goal was support of quality care initiatives. Twenty-one community sites in 16 states participated in the network providing care to approximately 40,000 cancer patients/year. We describe strategies for implementation of a structured quality program within our network. Methods: Four components served as the foundation for quality efforts: 1) increasing multidisciplinary care (MDC) programs; 2) ASCO QOPI participation; 3) Commission on Cancer Rapid Quality Reporting System (RQRS) participation; and 4) expansion of genetic counseling/services. A Quality of Care subcommittee formed to guide quality efforts within the network. Clinicians from the network served as subcommittee leadership and each site designated a quality of care lead. The subcommittee met by teleconference monthly, developed goals, shared best practices, developed processes to accomplish goals and documented improvements in priority areas. Results: Strategies employed to improve quality included: assessment tool development, participation in national quality reporting initiatives, review and monitoring of network data, and network performance improvement projects. Conclusions: The NCCCP identified areas of needed quality improvement. In addition, the network developed implementation strategies and created benchmarks that measure program quality. Participants benefitted from the opportunity to interface with one another and set network goals, while adopting strategies to best fit their own practices and community sites. [Table: see text]
Knockdown of Insulin Receptor Substrate 1 (IRS1); a Partner of BCR-ABL, Results In Decrease In Proliferation and Downregulation of AKT/mTOR and MAPK Pathways In K562 Cells
Authors: Joao Machado-Neto, Patricia Favaro, Mariana Lazarini, Fernando Ferreira Costa, Sara T. Olalla-Saad, Fabiola Traina
Journal: Blood (2010)
Phase II/III randomized trial of exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26).
Authors: Gilles Crehange, Franck Bonnetain, Didier Peiffert, Elisabeth Le Prise, Pierre-Luc Etienne, Emmanuel Rio, Renata Pereira, Georges Noel, Karen Benezery, Jean Francois Seitz
Journal: Journal of Clinical Oncology (2016)

TPS190 Background: INT 0123 failed to demonstrate an overall survival benefit with chemoradiotherapy dose escalation in locally advanced esophageal cancer. Nearly 45% of the patients had local persistent or recurrent disease. Several drawbacks surround the interpretation of the results of INT 0123. Improvements in target definitions with planning CT and 18 F FDG PET/CT in keeping with improvements in radiation dose delivery that better protect healthy tissues with 3D conformal radiation therapy and/or IMRT should lead to the retesting of dose escalation in the modern era of new technologies. Methods: Patients are randomized into two groups: Experimental group: 40Gy ENI followed by a 26-Gy boost to the primary tumor and involved nodes (i.e. 33 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Control group: 40Gy ENI followed by a 10-Gy boost to the primary tumor and involved nodes (in 25 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Randomization using minimization to ensure balanced allocation across: Center / Adeno vs Squamous cell carcinoma / stage III vs I-II / weight loss / 3D-CRT vs IMRT. The principal hypothesis is that the rate of survival without locoregional relapse at 2 years will reach 50% in the reference arm and 65% in the experimental arm (Hazard ratio = 0.62). With a risk α = 0.05 (bilateral test) and β = 0.15 (power 85%). If we use a rate of 5% for lost to follow-up, it will be necessary to recruit 266 patients. The main inclusion criteria are: age &lt; 75 years, WHO Status 0, 1 and 2, Enteral or parenteral feeding planned before the start of treatment if oral calorie intake &lt; 1500 kcal, Histologically proven carcinoma of the esophagus, adenocarcinoma or squamous cell, T3, N0-N3, M0 (UICC 7 th edition), T1-T2, N0-N3, M0 with a contra-indication for surgery, Absence of tracheo-esophageal fistula, Absence of thoracic or upper abdominal irradiation for another tumor, Written informed consent. 141 of the 160 patients required in phase II of the trial were included by September 22 nd 2015. (ClinicalTrials.gov Identifier: NCT01348217). Clinical trial information: NCT01348217.
Discussing treatment (Tx) and clinical trials for pancreatic cancer (PC): Learnings from the Pancreatic Cancer Action Network (PanCAN) survey.
Authors: Anitra Engebretson, Lynn Matrisian, Cara Thompson
Journal: Journal of Clinical Oncology (2015)

241 Background: In 2014, 46,420 patients (pts) in the US will be diagnosed with PC, and only 6.7% are expected to survive ≥ 5 years after diagnosis. Enrollment in clinical trials is recommended to improve pt outcomes. Methods: Funded by Celgene, PanCAN developed a 25-minute survey and distributed it online between 7/30/13 and 9/18/13 to pts with PC or caregivers whose loved ones were alive or had died of PC within the past 6 months. Results: Respondents included 184 pts (81 with metastatic PC) and 213 caregivers (145 for pts with metastatic PC). Pts and caregivers answered similarly with a few exceptions. Quality of life (QoL), extending survival, and symptom management were the 3 most important issues to all respondents. Caregivers placed statistically significantly more emphasis on QoL and managing symptoms vs pts (88% vs 71% and 68% vs 33%, respectively). A total of 196 respondents reported that Tx options were not offered at diagnosis, and 20% of these respondents stated that Tx options were never discussed with an MD. Most pts (95%) followed their doctors’ Tx recommendation, and 83% received chemotherapy. Almost half of respondents (49%) reported that their MD never discussed clinical trials; of those that did, oncologists (52%) were the primary source used to learn about possible clinical trial participation, followed by caregivers (16%) and loved ones (13%).Twelve percent of pts enrolled in clinical trials (&gt; the US average of 4.6%; J Clin Oncol 31:3432-3438). Forty-eight percent of respondents were aware of the Pt and Liaison Services (PALS) program, a support service from PanCAN. PALS-aware respondents were more likely than others to report that the pt had undergone chemotherapy (89% vs 78%), surgery (64% vs 41%), or radiation (47% vs 32%) and more likely to state that the pt followed a Tx recommendation because it was the best/most realistic option (19% vs 11%). PALS-aware pts also participated more often in clinical trials (15% vs 9%). Conclusions: These results underscore the importance of discussing Tx options, clinical trials, and support services with pts. Such steps could increase Tx and enrollment in clinical trials, possibly improving QoL, survival, and symptom management.
Laparoscopic lymphocele fenestration after retroperitoneal lymph node dissection in gynecological cancer patients: Safety, feasibilty, efficacy, and recurrence rates.
Authors: I. B. Runnebaum, M. P. Radosa, H. Diebolder, H. Winzer, J. Anschuetz, O. Camara
Journal: Journal of Clinical Oncology (2011)

e15502 Background: The occurrence of lymphoceles is a notorious complication occurring after retroperitoneal lymph node dissection (LND). In this largest series of patients with lymphoceles analyzed so far, we evaluated the technique of laparoscopic lymphocele fenestration in gynecologic cancer patients with history of a precedent retroperitoneal LND regarding safety and efficacy. Methods: From January 2001 to February 2008, surgical outcome was analyzed for 91 consecutive patients who underwent laparoscopic lymphocele fenestration for a symptomatic lymphocele, following retroperitoneal LND and retroperitoneal drainage from a total of 354 LND patients at our department during this time period. Results: A total of 118 lymphoceles were fenestrated. Mean duration of surgery was 119.6 minutes and the average intra-operative blood loss per patient was162.8 ml. Overall conversion rate to laparotomy was 8.8 %. The rate of major intraoperative or postoperative complication rate was 17.6 %, being significantly higher (23.8 %) in patients after pelvic and paraaortic LND compared to those after pelvic LND. Mean follow-up of the patients was 48.3 months. Two-year cumulative risk of lympohcele recurrence was 7.8% with a total of 7 recurrences of lymphoceles onserved. Conclusions: Laparoscopic lymphocele fenestration is a safe and effective surgical treatment option for symptomatic lymhphocele following pelvic or paraaortic LND in gynecological cancer patients. For laparoscopists, the technique can recommended as a standard treatment with an acceptable recurrence rate.
Predicting 10+ year survivors in total therapy 1 (TT1) for multiple myeloma (MM).
Authors: S. Waheed, Y. Alsayed, R. Sexton, A. Hoering, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8138 Background: The importance of marked tumor regression for long-term survival in MM is well appreciated. With a median follow-up in TT1 for 231 newly diagnosed patients with MM of 16 years, median overall survival (OS) and event-free survival (EFS) durations are 5.7 and 2.6 years, with 47 patients remaining alive and 25 event-free including 12 of 87 who had attained CR. The purpose of this investigation was to determine the baseline features that were independently linked to 10+ year OS and EFS, in the context of responsiveness (partial response, PR; complete response, CR) in the first year of therapy. Methods: Baseline and response levels were compared between ≤10yr and >10yr survivors and logistic regression applied to identify the critical features linked to >10yr OS and >10yr EFS status. Results: Among traditional baseline prognostic variables distinguishing >10yr survivors (lower frequencies of: CA; elevated levels of B2M, LDH and CRP; decreased hemoglobin; higher proportions of patients attaining CR and PR within 1yr), multivariate analysis identified PR as an independent favorable variable (OR = 3.32, p = 0.01) while adverse implications were observed for CA-13 status (OR = 0.08, p = 0.01), LDH ≥190U/L (OR = 0.39, p = 0.04) and CRP ≥4mg/L (OR = 0.48, p = 0.02). When examined by immunoglobulin isotypes (IgG, IgA, only light-chain), PR remained favorable for IgG (n = 130) along with adverse implications of any CA and of female gender; while CRP was the only variable surviving the model for IgA (n = 41); and no one variable identified >10yr survivorship in the 37 patients with only light chain disease. >10yr EFS was positively linked to CR (OR = 2.56, p = 0.02) and negatively to CRP > = 4mg/L (OR = 0.31, p = 0.01) Conclusions: Long-term >10yr EFS required CR and >10yr OS PR to have been achieved within the first year of therapy; with CRP elevation affecting both endpoints adversely, while LDH elevation and CA-13 status at presentation were additional negative features for >10yr OS. No significant financial relationships to disclose.
Branched evolution and intratumor heterogeneity of urothelial carcinoma of the bladder.
Authors: Eugene K. Cha, John P. Sfakianos, Hikmat Al-Ahmadie, Sasinya N. Scott, Philip H. Kim, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg, Michael F. Berger, Bernard H. Bochner, David B. Solit
Journal: Journal of Clinical Oncology (2014)

293 Background: Genomic characterization of urothelial carcinoma of the bladder (UCB) has begun to reveal significant intertumor heterogeneity when comparing samples from different subjects. As in other malignancies, intratumor heterogeneity, which may allow for tumor evolution and adaption, poses a significant challenge to personalized-medicine strategies. Methods: To examine UCB tumor evolution and heterogeneity, we performed next-generation targeted sequencing on multiple temporally and spatially separated bladder tumors obtained at time of transurethral resection (TUR) and radical cystectomy (RC). Specimens were analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 300 cancer-associated genes. Results: Phylogenetic reconstruction revealed evidence of branched evolutionary growth. Evaluation of multiple tumors from individual subjects identified both shared and unique potential driver mutations. Evidence of convergent phenotypic evolution was detected through analysis of multiple distinct tumors from several subjects. For example, three separate tumors in one subject shared a common PIK3CA mutation (E453K) and had unique second mutations in PIK3CA (E542V, E545K, and E545Q, respectively). In another subject, distinct inactivating mutations of EP300 were identified in two temporally separated tumor samples. Macrodissection of single tumors into non-invasive and invasive components revealed significant intratumor heterogeneity; one case illustrates how analysis of a muscle-invasive TUR specimen could result in undersampling and thereby miss the tumor clone that persisted at time of RC. Conclusions: We demonstrate branched evolution of UCB through genomic analyses of multiple temporally and spatially distinct bladder tumors from individual subjects. Macrodissection of individual tumor samples identified significant intratumor heterogeneity. These concepts may present major challenges to personalized-medicine approaches that rely on sampling of a single tumor at a specific timepoint in the evolution of a patient’s UCB.
Proportions of Bone Marrow Lymphocyte Subsets Predict Survival in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Independent of International Prognostic Index
Authors: Luke D. Zurbriggen, Jacob D Gundrum, Sai Ravi Kiran Pingali, Gorden G. Zeng, Austin Zeng, Linda J. Wright, Ronald S. Go
Journal: Blood (2008)
Confirmation of A Strong Relationship Between Race and Probability of Transplant Among Patients Referred for Hematopoietic Cell Transplantation (HCT) for Hematological Maliganancies – A 17 Year Experience
Authors: Manish Sharma, Thomas R Klumpp, John A Ulicny, Omotayo O. Fasan, Patricia Kropf, Mary Ellen Martin, Kenneth F. Mangan
Journal: Blood (2012)
Promyelocytic Extracellular Chromatin Exacerbates Coagulation Disorder in Acute Promyelocytic Leukemia
Authors: Muhua Cao, Ruishuang Ma, Xiaoming Wu, Lixiu Wang, Lu Zhao, Yan Zhang, Zhipeng Yao, Tao Li, Junjie Kou, Yayan Bi, Jin Zhou, Jialan Shi
Journal: Blood (2016)
Detection of Leukemic Phase in Patients with Follicular Lymphoma At Diagnosis: A Rare Event Associated with Poor Prognosis
Authors: Clémentine Sarkozy, Lucile Baseggio, Evelyne Callet-Bauchu, Lionel Karlin, Laure L Lebras, Anne-Sophie Michallet, Olivier Dumas, Alexandra Traverse-Glehen, Francoise Berger, Bertrand Coiffier, Pascale Felman, Gilles Salles
Journal: Blood (2012)