tbuckley/cabot-search huggingface dataset:
Results of a phase II study of sunitinib (SU) maintenance after response to docetaxel in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Bernhard J. Eigl, Misha Eliasziw, Scott A. North, Marc G. Trudeau, Eric Winquist, Kim N. Chi, Joseph D. Ruether
Journal: Journal of Clinical Oncology (2013)

153 Background: Docetaxel (D) remains the standard first cytotoxic therapy in mCRPC. Given its mechanism of action, acceptable toxicity profile and simple administration, SU had potential as maintenance therapy for mCRPC. In this multicenter study, we evaluated the tolerability and efficacy of SU monotherapy in patients (pts) with mCRPC who have responded to D. Methods: Pts withmCRPC and responding/stable disease at the time of D completion were enrolled in this multicentre trial. Pts received 50mg of SU daily on 4/2 week on/off cycles. The primary endpoint was progression-free survival (PFS), defined on the basis of RECIST criteria and worsening disease-related symptoms requiring further therapy. Because the effect of SU on PSA is not well known, PSA progression alone was not considered disease progression. PFS of 180 days was considered to be a clinically meaningful threshold for recommending further study of SU. PSA response was a secondary endpoint. The threshold for PSA-progression (PSA-P) was defined as a 25% increase in PSA over baseline. Results: Twenty-three pts were enrolled and treated. Mean age was 66.5 years (48-78). ECOG scores of 0, 1, and 2 were reported for 9, 13 and 1 pts respectively. Mean number of prior cycles of D was 8.6 (4-12). A total of 92 cycles of SU were administered; a mean of 4 per pt (1-11). Mean follow-up was 5.4 months (0.6-15). A total of 479 adverse events (AE) were recorded, of which 88% were Grade 1-2 and 12% were Grade 3-4. The AE were of a type and severity expected for SU. Three Grade 4s occurred, consisting of hepatitis, myelosuppression, and pneumonia. Median PFS was 133 days (95% CI: 48-154). Most pts had immediate PSA increases without evidence of disease progression, with the mean increases in PSA over baseline being 197%, 342%, and 1437% in Cycles 1, 2, and 3, respectively (p&lt;0.05). Conclusions: Although SU was well tolerated as maintenance therapy with predictable side-effects, median PFS was lower than the predefined threshold of 180 days. PSA values were not informative as significant increases were observed as early as Cycle 2. This agent is not considered worthy of further investigation in this setting of maintenance therapy. Clinical trial information: NCT00550810.
Early diagnostic value of survivin and its alternative splice variants in breast cancers.
Authors: Salma Khan, Yuan Yuan, Malyn May Valenzuela, David Turay, Heather Ferguson, Siu-Fun Wong, Mia Perez, Saied Mirshahidi, Nathan R Wall
Journal: Journal of Clinical Oncology (2012)

35 Background: The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues and have recently been shown to be released from tumor cells via small membrane-bound vesicles called exosomes. Tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions by impacting immune escape, tumor invasion and angiogenesis. We, therefore, hypothesize that analysis of exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer in addition to current recommended methods. Methods: Twenty paired breast cancer patient’s sera and tumor tissue, and ten normal control sera were used for analysis. ELISA was performed to quantitate serum levels of Survivin. Exosomes were isolated from the sera using Exoquick. RT-PCR, western blots with densitometry, and immunohistochemistry followed by confocal microscopy were then performed. Results: For each breast cancer patient serum, Survivin levels were significantly higher compared to control (p&lt;0.05). While Survivin and the DEx3 splice variant expression and localization were similar, differential expression of Survivin and the 2B splice variant protein and mRNA existed in the exosomes and tissue samples. Survivin and -DEx3 proteins were the predominant forms detected in 100% (20/20) of the breast cancer tissues evaluated, whereas a more variable expression of Survivin-2B, with enhanced levels found in areas of necrosis. We also for the first time here show the exosomal localization of Survivin and its splice variants DEx3 and 2B in sera from breast cancer patients. Conclusions: The result of the proposed project supports our hypothesis that differential expression of exosomal-Survivin and its alternative splice variants may serve as a diagnostic marker in breast cancer patients. For future direction, we plan to study the prognostic value of exosomal-Survivin and its splice variants on a large panel of primary breast cancers within a setting of well-followed clinical outcomes.
Method of biopsy and sample quality for genetic mutation testing in advanced non-small cell lung cancer in a community hospital.
Authors: Borys Hrinczenko, Subramony Subramonia-Iyer
Journal: Journal of Clinical Oncology (2012)

271 Background: Mutated EGFR gene testing transformed the care of NSCLC. ASCO now recommends EGFR mutation testing for NSCLC (April 2011); however, no studies to assess quality of biopsy samples and adequacy for mutation testing have been done outside a trial setting. Methods: A retrospective chart review to identify patients diagnosed with NSCLC at a community hospital during 2010. A pathologist reviewed the quality of archivedbiopsy samples for histological diagnosis and adequacy for EGFR mutation testing based on ASCO criteria. Results: In 2010, 64 cases of NSCLC were diagnosed and 18 patients had definitive surgery, 46 did not. Histological subtypes: squamous - 28 (44%), adenocarcinoma - 23 (36%), bronchoalveolar - 3 (5%), adeno with mixed bronchoalveolar - 2 (3%), large cell - 3 (5%), and large cell neuroendocrine - 2 (3%). Staging: stage I, II, III, IV - 18 (28%), 2 (3%), 13 (20%), 23 (36%). Biopsy material: transbronchial needle biopsy in 23 (36%), CT-guided biopsy in 13 (20%), surgery in 18 (28%), other - 10 (15%). Specimen review: 3 samples (5%) were designated as large cell carcinoma without squamous or adeno specification. 46/64 (72%) were adequate for mutation analysis; 18 (28%) were not. Among adenoca., 19/28 (68%) were adequate samples, but 9 (32%) were not. Among the 46 patients who had advanced or metastatic disease, 28 (60%) had sufficient samples, 18 (40%) did not. Among advanced adenoca. patients, the proportion without adequate sample was 9/18 (50%). Route of biopsy: 4/23 transbronchial biopsies (17%), 8/13 CT-guided biopsies (62%) and 6/10 from other sites (60%) were inadequate (p = 0.01). Conclusions: Nearly one-third of all NSCLC cases, including half of advanced adenoca., yielded poor quality specimens from the first biopsy for EGFR mutation analysis. 5% of samples lacked definitive histology. CT-guided transthoracic biopsies were at least twice as likely to yield poorer quality specimens compared to transbronchial biopsies. Poor quality tumor sampling may preclude mutation testing thus denying beneficial and less toxic therapy. Quality of tumor specimens needs to be improved in the future by the development of appropriate strategies by multidisciplinary lung cancer teams.
Cost-effectiveness of nilotinib versus imatinib as first-line treatment for newly diagnosed patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in the chronic phase (CML-CP): Swedish perspective.
Authors: A. Ovanfors, J. Stephens, S. J. Snedecor, D. Patel, X. Ji, K. T. Carpiuc, J. Coombs, M. Botteman
Journal: Journal of Clinical Oncology (2011)

6572
A "continuously connected team support" model to facilitate high-quality gynecologic cancer care in rural and remote regions.
Authors: David F. Silver, Steven M. Aukers, Melissa A. Simon
Journal: Journal of Clinical Oncology (2014)

51 Background: Quality gynecologic cancer care (GCC) in rural and remote regions (RRR) of the U.S. is limited by poor access to gynecologic oncology expertise (GOE). While a variety of telehealth programs in other specialties have enhanced healthcare in RRR, none have resulted in provision of the comprehensive medical and surgical services required to treat gynecologic cancer patients. We propose a model to improve access and quality for comprehensive GCC in RRR. Methods: PubMed, Medline, and Google searches identified and characterized: 1) core quality components of GCC models; 2) RRR lacking GOE; and 3) current models for delivering healthcare services in remote regions. A new model was developed addressing needs of RRR. Results: Characteristics observed in high-performing GCC models include: 1) gynecologic oncologists (GO) guide all aspects of GCC, 2) care is performed by high-volume providers (HVP), and 3) multidisciplinary provider teams (MDT) address all patient needs. Without equal access to GO, HVP, or MDT, patients in RRR do not share benefits of high-quality outcomes. Integrating components of successful telementoring models with identified high-quality characteristics of traditional GCC, our model is developed to address the comprehensive and ongoing unique GCC needs of RRR. This Continuously Connected Team Support (CCTS) model utilizes a semi-remote GO to facilitate quality GCC through mentorship and education of a local MDT, transforming it into a transdisciplinary team (TDT). Off-site activities include 24/7 availability via phone or HIPAA-compliant videoconferencing. The GO’s on-site activities include proctoring the TDT in surgeries, mentoring and educating in clinical conferences, and continuous quality improvement activities. Long-term, regular on-site and remote interactions with the local TDT makes CCTS unique in its commitment and service beyond that of itinerant surgeons, locum tenens, international surgical charity efforts or established telehealth programs. Conclusions: Deployment of CCTS in RRR offers an innovative solution for the facilitation of high-quality comprehensive GCC in RRR lacking GOE. Further outcomes research is warranted.
Evaluation of a predictive staging model for Kaposi sarcoma in Uganda.
Authors: Fred Machyo Okuku, Warren Phipps, Elizabeth Krantz, James Kafeero, Jackson Orem, Moses Kamya, Corey Casper
Journal: Journal of Clinical Oncology (2015)

e21528 Background: HIV-associated Kaposi sarcoma (KS) is commonly staged using the AIDS Clinical Trials Group criteria, which classify 3 variables-- tumor extent (T), immune status (I), and systemic symptoms (S)  into good risk (0) and poor risk (1). Although validated in the US and Europe, these criteria have not been evaluated in sub-Saharan Africa (SSA), where the burden of KS is greatest. Methods: We reviewed medical charts ofadult patients with HIV-associated KS seen at the Uganda Cancer Institute from 2001-2006. Vital status at 2 years after KS diagnosis was determined from the medical chart, or by contacting the patient or next of kin. Survival estimates used Kaplan-Meier (KM) methods. Two-thirds of the data were randomly selected to develop a predictive Cox model, while one-third were reserved for validation. Due to violations of proportional hazards, predictors were evaluated for 2 periods: 0-4 months and 4-24 months after KS diagnosis, which generally correspond to periods of initial chemotherapy and follow-up. The model's predictive ability was assessed by computing the area under the curve (AUC). Results: At 2 years after KS diagnosis, 167 (41%) patients were alive, 156 (39%) had died, and 81 (20%) were lost to follow-up. The KM estimate of 2-year survival was 57%. Survival curves differed significantly by T (p < 0.001) and by S (p < 0.001), but not by I (p = 0.57). S1 was associated with death in months 0-4 [HR 6.4, 95% CI (1.9-21.1)], while T1 was associated with death in months 4-24 [HR 4.0, 95% CI (1.4-11.5)]. Immune status was not associated with survival. The ability to classify survival status using model-predicted probabilities was limited (AUC at 4 months, 1 year, 2 years: 0.60, 0.53, 0.51). Conclusions: Systemic symptoms were strongly associated with death in the early period after KS diagnosis, while tumor status was most predictive of death in the 4-24 month period. CD4 count did not predict survival. These findings suggest that different biologic processes may influence outcomes in the early and late periods following KS diagnosis, which may indicate a need for different treatment strategies among KS patients at high risk for early death. Further studies are needed to confirm this observation and to identify better predictors of KS survival in SSA.
Intermediate versus short-course hormone therapy and mortality in men with high-risk prostate cancer treated with radiation therapy.
Authors: Akash Nanda, Ming-Hui Chen, Brian Joseph Moran, Michelle H. Braccioforte, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2013)

83 Background: Radiation therapy (RT) plus 28-36 months of hormonal therapy (HT) is standard-of-care for men with high-risk prostate cancer (HRPC) based on randomized trials comparing these HT durations to 4-6 months. However, it is unknown whether shorter durations of HT may also decrease mortality. We evaluate the impact of intermediate-course HT on the risk of all-cause mortality (ACM) in men with HRPC treated with RT. Methods: The study cohort comprised 554 men with HRPC (PSA &gt; 20; Gleason score 8 or higher; or clinical stage T2c or higher) consecutively treated at the Chicago Prostate Cancer Center between 1997 and 2007. All men received brachytherapy with or without external beam RT and HT of intermediate (&gt; 6 to 24; median 12 months) or short (up to 6; median 4 months) duration. A Cox regression multivariable analysis was performed assessing whether intermediate compared to short-course HT was associated with a decreased risk of ACM, adjusting for age, year and type of RT, treatment propensity score, and known PC prognostic factors. Results: After a median follow up of 4.3 years a total of 64 (11.6%) men died. Intermediate compared to short-course HT was associated with a significantly decreased risk of ACM (adjusted hazard ratio 0.44, 95% confidence interval 0.20 - 0.94, P = 0.03). Other significant covariates are shown in the table. The 5-year estimates of ACM for intermediate versus short-course HT were 7.0% and 15.7%, respectively. Conclusions: In men with HRPC treated with RT, a median HT duration of 12 months was associated with a significantly decreased risk of ACM when compared to a median HT duration of 4 months. This raises the hypothesis that HT durations shorter than 28-36 months may be sufficient to decrease mortality in men with HRPC. The ongoing RADAR trial by the Trans Tasman Radiation Oncology Group comparing 18 to 6 months of HT may provide level I evidence to validate this hypothesis. [Table: see text]
Single ROI Versus Multislice T2* MRI Approach for the Quantification of Hepatic Iron Overload
Authors: Antonella Meloni, Antongiulio Luciani, Vincenzo Positano, Daniele De Marchi, Gianluca Valeri, Gennaro Restaino, Gaetano Roccamo, Sabrina Armari, Maria Chiara Dell'Amico, Brunella Favilli, Alma Lippi, Massimo Lombardi, Alessia Pepe
Journal: Blood (2010)
ZAP-70 Expression in T Cells of B-Cell Chronic Lymphocytic Leukaemia: Correlation with Negative Prognostic Factors of the Disease.
Authors: Donatella Raspadori, Maristella Tassi, Mariapia Lenoci, Deborah Bravi, Maria Antonietta Dell’Aversano, Francesco Forconi, Francesco Lauria
Journal: Blood (2005)
Real world chart review of adverse event management in patients taking tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) by line of therapy (LoT).
Authors: Sandhya Srinivas, Dara Stein, Dana Y Teltsch, Sunning Tao, Krishnan Ramaswamy
Journal: Journal of Clinical Oncology (2016)

521 Background: This is the first real world study to describe adverse events of special interest (AESI) management for all available TKIs by LoT. A better understanding of optimal AE management can positively impact patient care. Methods: A chart review was conducted largely in community oncology practices in Canada and the US. Patients with mRCC were eligible if they started TKI monotherapy between Nov 15, 2010-Nov 15, 2013 and had ≥ 1 of 5 AESI onset ≤ 3 months post TKI start. AESI included fatigue, hypertension, diarrhea, hand-foot syndrome and stomatitis/mucositis. Data on patient demographics, medical history, drug regimen, and AESI management were collected. Results: 220 patients from 27 centers were included. 63% of patients received TKI in 1 st , 22% in 2 nd and 15% in 3 rd LoT. TKIs included axitinib (9%), pazopanib (27%), sorafenib (8%) and sunitinib (55%). 376 AESI occurred in 220 patients; 87% were non-serious. Fatigue (62%), hypertension (37%), diarrhea (31%), stomatitis/mucositis (29%), and hand-foot syndrome (12%) were reported. 55% of AESI resolved/were resolving within 3.5 months of onset. 8% of patients received AESI prophylaxis (Px) and 59% received treatment (Tx). Incidence of stomatitis/mucositis declined as LoT progressed (37%, 16%, 12%). More patients in 1 st vs. ≥ 2 nd LoT had AESI related TKI discontinuation (17% vs. 12%), interruptions (17% vs. 12%) and reductions (43% vs. 32%). Fewer patients missed doses as LoT progressed (38%, 25%, 18%). Fatigue was the commonest AESI across LoT, and fatigue as a reason for therapy delay/interruption increased across LoT (7%, 14%, 50%). The rates of Tx or Px for fatigue remained low across LoT. Rates of AESI Px were low across the LoT (10%, 0.4%, 0.3%). More patients in 1 st (61%) received AESI Tx vs. 2 nd (47%) LoT. Conclusions: Most AESI were non-serious, and over half of patients received some form of AESI Tx. Fatigue was the most common yet least frequently Tx AESI. Very few patients received Px across LoT. More patients in 1 st versus 2 nd LoT experienced dose modifications/discontinuation and received AESI Tx. More emphasis on Px/Tx options for non-serious bothersome AEs is warranted.
Results of a phase I/II study of the combination of 5-aza-2’-deoxycytidine and valproic acid in patients with acute myeloid leukemia and myelodysplastic syndrome
Authors: G. Garcia-Manero, H. Kantarjian, B. Sanchez-Gonzalez, S. Verstovsek, F. Ravandi, M. Ryttling, J. Cortes, H. Yang, J. Fiorentino, G. Rosner, J.-P. Issa
Journal: Journal of Clinical Oncology (2005)

6544
The cost-effectiveness of primary prophylaxis with granulocyte colony-stimulating factor in docetaxel-containing adjuvant chemotherapy in early breast cancer: The impact of risk of febrile neutropenia and its mortality.
Authors: K. K. Chan, M. E. Trudeau, A. Eisen, J. L. Verreault, C. A. Freedman, S. Dent
Journal: Journal of Clinical Oncology (2011)

6086 Background: Studies have shown higher rates of febrile neutropenia (FN) with docetaxel (D) containing chemotherapy (C) in early breast cancer (BC) patients than those in clinical trials (CTs). Previous cost-effectiveness analyses (CEA) on FEC-D vs FEC and primary prophylaxis (PP) of granulocyte colony stimulating factor (GCSF) were based on FN risk from CTs that may not reflect the real world. These CEA lacked the complexity to model the risk of FN per cycle, address use of PP vs secondary prophylaxis (SP) & examine long term efficacy of FEC-D vs FEC jointly. Methods: A 2-stage Markov model was developed for a hypothetical cohort of patients age 50 with early BC. First stage modeled costs/outcomes of 6 cycles C (FEC or FEC-D), including events related to FN, complications and G-CSF use (either PP or SP). Second stage modeled costs/outcomes of local/distant relapse, and death from BC (10 year horizon). Efficacy data of C and G-CSF, and utility were obtained from published data. Model was based on 3rd party payer (2010 Canadian dollars - 3% discounting rate). 4 strategies were used: (S1) FEC x 6 with SP, (S2) FEC x 3 with SP → D x 3 with SP, (S3) FEC x 3 with SP → D x 3 with PP, (S4) FEC x 3 with PP → D x 3 with PP. Results: At a willingness-to-pay (WTP) threshold of $50,000/QALY, S2 is preferred to S1 when risk of FN with D per cycle without G-CSF is < 9%, 6% or 4% if risk of death from FN is 1%, 5% or 10% respectively. S3 may be preferred if the risk of death from FN is > 14%. At a WTP of $100,000/QALY, S3 is preferred to S2 when risk of FN with D per cycle is > 12%, 4% or 2% if the risk of death from FN is 1%, 5% or 10% respectively. S4 is preferred to S3 only if risk of death from FN is > 18%. S1 is preferred only if risk of FN with D per cycle is much > 40%. Conclusions: We developed an economic model to determine the cost-effectiveness of different C/GCSF strategies in early BC, calibrated to the efficacies reported in CTs. In the “real world”, the most cost-effective strategy will depend on accurate understanding of the risk of developing/dying from FN in the non CTs setting. Societal WTP threshold will have a significant impact on defining the optimal systemic approach.
Monitoring of the CD3+CD8+/CD4+CD25+FoxP3+ ratio in PBMC in colorectal chemotherapy patients.
Authors: T. Sasatomi, Y. Ogata, K. Shirouzu, H. Yamana
Journal: Journal of Clinical Oncology (2011)

e14160 Background: Many multiple anti cancer drugs regimens have been established for recurrent colorectal cancer chemotherapy recently. We investigated cellular immuno-reaction of these patients to their cancer. Methods: From September 2008 to October 2010, 22 recurrent colorectal cancer patients after surgery have been started standard chemotherapies. Chemotherapies were bevacizumab + mFOLFOX6 or cetuximab + FOLFIRI (FOLFOX: 5FU+LV+Oxp, FOLFIRI: 5FU+LV+CPT-11). Their PBMC (peripheral blood mono nuclear cell) were harvested and investigated their character by FACScan (fluorescence-activated cell sorter scan) with fluorescent labeled antibodies (CD3, CD8, CD4, CD25, Foxp3). CTL (cytotoxic T cell: CD3+, CD8+) and T reg (regulatory T cell: CD4+, CD25+, Foxp3+) were analyzed at before and after chemotherapy. Results: After chemotherapy, both CTLs (cytotoxic T cell: CD3, CD8 positive) and T regs (regulatory T cell: CD4, CD25, Foxp3 positive) were decreased in number among tumor marker decreased patients. Both CTLs and T regs were also decreased in number among tumor marker increased or stable patients. On the other hand, CTL/T reg Ratio were significantly increased among tumor marker decreased patients and significantly decreased among tumor marker increased or stable patients (p=0.0425). Conclusions: We found that the CTL/T reg Ratio of PBMC in colorectal cancer patients with chemotherapy were useful method for expectation of chemotherapy.