tbuckley/cabot-search huggingface dataset:
Using a pathways process to ensure measurable evidence-based standardized care in a large cancer network.
Authors: Peter G. Ellis, Kathleen Lokay
Journal: Journal of Clinical Oncology (2012)

252 Background: UPMC CancerCenter includes 40 sites of services in a 100 mile radius in Western Pennsylvania. Consistency and quality of care are critical to such a diverse network. In addition, the UPMC mission includes accrual to clinical trials. To meet these challenges, UPMC developed the Via Oncology Pathways. The program has served UPMC well for over seven years to date and is now a key foundation for UPMC’s overall healthcare reform strategy for quality and accountable care. Methods: Treatment algorithms were developed for 90% of cancer types by establishing committees of academic and community specialists. These committees interpret the literature and define the most efficacious, least toxic, and economically efficient treatment regimens appropriate for highly specific disease presentations (e.g., node +, er-, her2 +, PS 0-1). Clinical trials are also imbedded into the algorithms. Quarterly, these algorithms are reviewed by the committees to assess relevance, review network feedback, add newly available trials and address emerging data. Equally important to clinical content is its presentation to the practicing physician in a manner that allows real time usage and adds value to physician workflow. This is accomplished with a web portal that presents the individual pathways status through the physician’s daily schedule. Results: Over 120 oncologists at UPMC use Via Oncology Pathways in their daily practice. In 2011, UPMC physicians confirmed a pathways status for 94% of their patient visits (195,000) and achieved an On Pathway rate of 82% for their 18,000 treatment decisions. The database also includes patient presentations, reasons for going off pathway and reasons for not accruing to clinical trial. Lower hospitalization rates and mandated adoption of personalized medicine were also observed. Conclusions: When appropriately developed and implemented, clinical pathways are a solution to improving the quality and cost effectiveness of cancer care by enhancing physician decision-making, standardizing care and ensuring access to evidence-based personalized medicine. We continue to expand the scope of our pathways to include diagnostic studies, surveillance protocols and end of life prompts.
Phase I trial of imexon (IMX) in patients (pts) with advanced solid tumors
Authors: T. Dragovich, D. Mendelson, M. Gordon, K. Long, M. Downhour, R. Dorr, E. Hersh
Journal: Journal of Clinical Oncology (2005)

3153 Background: IMX is a non-myelosuppressive, iminopyrrolidone agent which overcomes multi-drug resistance and induces cytotoxicity by depleting cellular thiols, inducing oxidative stress, causing mitochondrial damage, leakage of cytochrome C and apoptosis. Methods: In the current phase I study, IMX was given by a 30 minute IV infusion daily for 5 days every other week. Dose levels were 20, 40, 80, 105, 140, 185, 245, 325, 430 and 570 mg/m2 per day. In an accelerated dose escalation scheme 1 - 6 pts were enrolled per each dose level. A total of 30 pts have been treated; 7 with pancreatic cancer, 7 with melanoma, 4 with ovarian, 2 each with NSCLC and endometrial, and 1 with prostate, hepatocellular, breast, colon, renal, squamous cell, head and neck, and sarcoma. Results: The median number of courses administered was 3.5 (7 weeks) for patients receiving 20- 40 mg/m2, and 4 (8 weeks) for those receiving 185 - 570 mg/m2 of IMX. No ≥grade 3 drug-related toxicity has been observed through 570 mg/m2 dose. Grade 1/2 toxicities included constipation, nausea, fatigue, and skin rash (1 pt). There was no myelosuppression or neurotoxicity. Preliminarily, at the 105 mg/m2 dose, the peak blood level of IMX was 15 μcg per ml with T½ of approximately 30 minutes. Plasma thiol levels remained unchanged up to the 570 mg/m2 dose level. Of 26 pts who received at least 2 courses of IMX six achieved disease stabilization lasting > 3 months. No objective responses were seen. Conclusions: IMX therapy was well tolerated and resulted in some preliminary anti-tumor activity. The MTD has not been reached yet and the dose escalation continues at 750 mg/m2 dose. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amplimed Amplimed
Nurse-lead clinics for capecitabine: A prospective audit evaluating changes in toxicity profile and efficacy.
Authors: L. M. Samuel, D. Lynch, G. Christie, J. Collie, N. McLachlan, J. Jordan, A. Macdonald, P. Gent
Journal: Journal of Clinical Oncology (2011)

564 Background: Oral chemotherapy offers patients equal efficacy but fewer visits to hospital and less time spent traveling, but there are concerns about toxicity and compliance. Nursing and physician interactions with patients are different, and when a nurse-lead oral chemotherapy service was developed in NE Scotland in 2003 a prospective audit was begun to monitor safety and efficacy. Methods: Patients with colorectal cancer who declined or were not eligible for appropriate clinical trials had their course of adjuvant or palliative capecitabine chemotherapy prospectively monitored through a nurse-lead clinic. At every clinic visit data was collected on patient demographics, blood and imaging results, and adverse events (AEs). Any decision to change dose was made by the colorectal oncology medical staff. Results: From September 2003 to November 2006 there were 177 patients prospectively monitored through the nurse-lead clinics. Palliative patients (n = 100), median age 69 (range 43-89) and majority PS 0 or 1. Initial dose reduction in 30% due to low GFR and 13% due to being &gt;75 years old. Overall 77% of patients completed on the starting dose. AE's, shown in table, and efficacy compared with capecitabine registration data (younger age group). Median overall survival 47.7 weeks (cf 56.6 weeks). Adjuvant patients (n = 77), median age 64 (range 40-88) and all PS 0 or 1. Initial dose reduction in 19% due to low GFR and 2% due to being &gt;75 years old. Overall 58% completed on the starting dose (= X-ACT study). AEs, other than 5% G3/4 lethargy, and efficacy similar when compared with X-ACT data, including 3 year DFS of 64% (cf X-ACT 64%). Conclusions: Using nurses to assess patients receiving capecitabine does not seem to significantly alter efficacy but does alter the AE profile compared with the registration data, particularly in the palliative patients. Differences in the nurse-patient relationship with nurses seen as less busy, more approachable and not taking treatment decisions can improve the quality of care in patients receiving capecitabine chemotherapy. [Table: see text] [Table: see text]
Chemotherapy (CT) treatment patterns and neutropenia management in gastric cancer patients (pts) receiving myelosuppressive chemotherapy in Europe.
Authors: Ewa Kalinka-Warzocha, Javier Gallego Plazas, Laurent Mineur, Tomas Salek, Alain Hendlisz, Kate Bendall, Florian D. Vogl, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2013)

128 Background: Granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (PP) is recommended for pts undergoing CT who are at overall high risk for febrile neutropenia (FN). No single CT regimen is recognized as standard in gastric cancer and few regimens are represented in G-CSF guidelines. We therefore evaluated neutropenia management in pts receiving CT for gastric cancer. Methods: This was a multicentre prospective observational study that enrolled pts sequentially from 11/2009 to 06/2011. Adult gastric cancer pts (any stage) with ≥3 cycles of myelosuppressive CT scheduled and an investigator-assessed overall FN risk ≥20% were eligible. The primary outcome was the proportion of pts who received PP G-CSF (G-CSF in days 1-7 of cycle 1). Secondary outcomes included FN incidence, chemotherapy administration, and G-CSF use. Posthoc analyses investigated the subgroup who received DCF, including modifications from standard DCF (Van Cutsem. JCO. 2006), and the G-CSF support given up to the first FN (G-CSF prophylaxis given per label in each cycle up to that in which FN occurred). Results: Of 209 pts enrolled, 199 were eligible and their data analyzed. The mean (±SD) age was 62 (±12) years, 76% were male, 17% were ECOG 2 and none ECOG 3-4; 47% were treatment naïve. Planned CT was palliative in 74% of pts; overall, 27 different backbone regimens were planned (10 triplet, 12 doublet, 5 single drug regimens). The most common regimen used was DCF (54 pts, 27%), predominantly given as modified DCF (41 pts). Despite being assessed as high risk for FN, G-CSF PP was administered to only 35% of pts overall (n=70; 54 pegfilgrastim, 16 daily G-CSF) and to 69% of pts who received DCF. FN occurred in 14 pts (10%), 9 of whom received DCF. A large majority of FN pts (12/14, 86%) had not received prophylactic G-CSF per label up to the first FN occurrence; furthermore, 86% of FN pts did not receive G-CSF prophylaxis in the cycle following the FN event. Conclusions: The variety of CT used, frequent modifications to standard CT, and presence of pt risk factors makes FN risk estimation difficult in gastric cancer. Improved risk assessment and appropriate targeting of G-CSF PP to high risk pts is needed.
A dose-escalating and pharmacodynamic study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and radiation in patients with locally advanced pancreas cancer.
Authors: L. K. Martin, G. Jia, X. Yang, J. C. Grecula, E. J. Harper, C. Kefauver, L. Wei, Z. K. Shah, M. Bloomston, W. S. Melvin, P. Muscarella, E. C. Ellison, M. V. Knopp, I. Espinoza Delgado, M. R. Grever, T. S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2011)

e14558 Background: Pancreas cancer is a leading cause of cancer death in the US. Chemoradiation, a standard therapy for patients with locally advanced pancreas cancer (LAPCA), has resulted in modest improvement in outcome. Triapine, an inhibitor of the M2 subunit of ribonucleotide reductase, was shown to be a radiosensitizer in preclinical and early clinical studies. Methods: This is a dose escalation trial with three dose levels of triapine (24 mg/m2, 48 mg/m2, 72 mg/m2) administered concurrently with a total of 50.4 Gy of radiation in 28 fractions. Patients with LAPCA were given triapine intravenously over 2 hours, within 30 minutes of radiation, every Monday Wednesday and Friday, every other week for 5 ½ weeks. The primary endpoint was to determine the maximum tolerated dose (MTD) of triapine in combination with radiation. Secondary endpoints included response and radiographic correlates with dynamic contrast enhanced (DCE) MRI. Results: Eleven patients were treated. Three patients were non-evaluable (NE) for the primary endpoint due to disease progression prior to completion of therapy (2) or other (1). Four patients (1 NE) were enrolled at dose level 1, 3 patients at dose level 2, and 4 patients (2NE) at dose level 3 with the fourth patient still undergoing treatment. A fifth and last patient is scheduled to begin treatment at dose level 3, which is the highest planned dose level. No DLTs have been observed so far. The only related grade 3 toxicity was thrombocytopenia in 1 patient at dose level 2. Two of ten (20%) patients evaluable for response achieved a PR. One patient underwent successful surgical resection after therapy. mPFS is 4 months (95% CI 1-10) and mOS 7.5 months (95% CI 3-15.8). DCE MRI was shown to be a potential early predictor for response to therapy in LAPCA. Conclusions: The combination of triapine and radiation is safe and tolerable in patients with LAPCA with evidence of preliminary activity. DCE MRI is a potentially useful imaging tool to predict early response to therapy in patients with LAPCA and deserves further investigation. Final results including the recommended phase II dosing will be presented at the meeting.
miR-194-5p/BCLAF1 deregulation in AML tumorigenesis
Authors: C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V Belsito Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
Journal: Leukemia (2017)

Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.
Meta-analysis of randomized trials to study the impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer.
Authors: Gurudatta Naik, Charity Morgan, Matt D. Galsky, William K. Oh, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

28 Background: The impact of daily oral prednisone (P) on toxicities and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) is unclear. We conducted a meta-analysis of randomized trials comparing regimens that included P in only one arm. Methods: PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2013. Eligible studies were selected in an unbiased manner and limited to randomized trials enrolling patients with mCRPC and comparing regimens administering P in only one arm. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Arms containing P were compared with arms without P for severe toxicities grade 3 or higher and overall survival (OS). Results: Five randomized trials were published or presented with P in only one arm: by Scher and colleagues comparing docetaxel (D) plus P versus D plus DN101 (n=953), by Higano and colleagues comparing DP versus GVAX (n=621), by Small and colleagues comparing DP versus GVAX plus D (n=394), by Fossa and colleagues comparing P versus flutamide (n=201) and by Petrylak and colleagues comparing mitoxantrone plus P versus D plus estramustine phosphate (n=770). The total number of patients was 2,939, of whom 1,471 received therapy not containing P and 1,468 received therapy containing P. All five trials were eligible for analysis of toxicities, but the Fossa trial was excluded for the OS analysis due to lack of required parameters. There was no difference between the non-P and P groups for severe toxicities (incidence rate ratio [IRR] = 0.82, p = 0.712, I 2 = 97.9%). When examining toxicities as a reason for discontinuing therapy, the non-P groups were not different from the P groups (relative risk [RR] = 1.24, p = 0.413, I 2 = 86.8%). The non-P groups demonstrated no difference in OS compared to the P groups (HR = 1.09, p = 0.531, I 2 = 79.7%). The meta-analysis is limited by the trial level design and small number of patients and does not exclude a favorable palliative impact of P. Conclusions: This meta-analysis of randomized trials in mCRPC suggests no significant impact on severe toxicities and OS with the use of daily oral prednisone.
Radiation in the management of pancreatic neuroendocrine tumors.
Authors: Bertram W. Maidment, Trevor Ellison, Joseph M. Herman, Navesh K Sharma, Dan Laheru, William Regine, Aaron Tyler Wild, Kelly Olino, Ralph H. Hruban, John L Cameron, H. Richard Alexander, Nader Hanna, Petr Frantisek Hausner, Lei Zheng, Michael A. Choti, Richard D. Schulick, Christopher Lee Wolfgang, Barish H Edil
Journal: Journal of Clinical Oncology (2012)

335 Background: Radiation therapy (RT) has not historically been incorporated into multidisciplinary management of pancreatic neuroendocrine tumors (PNTs). We provide a two-institution series of patients with PNTs who were treated with external beam RT either neoadjuvantly to attempt down-staging for surgery, or in the setting of post-surgical recurrence. Our objective was to assess treatment response and outcomes in this cohort of patients. Methods: We identified eleven patients with a pathologic diagnosis of PNT from 2006-2011 who received external beam RT to the primary tumor or resection bed. Each institution’s electronic medical record was used to evaluate patient demographics, disease characteristics, treatment regimens and tolerance, radiographic response, and survival. Results: Our series consists of eleven patients (6 men, 5 women) with a mean age of 57 years (range 37-72 years). All had biopsy proven PNT and were clinically T3 (n=3) or T4 (n=8), M0. Five patients were clinically node positive. All patients received RT to the primary tumor or resection bed to a median dose of 50.4 Gy. Seven patients received concurrent chemotherapy with capecitabine at a median dose of 1000mg/m 2 bid. Nine patients were treated definitively for locally advanced disease, two of whom subsequently underwent surgical resection. Two patients were treated to palliate post-resection recurrence. Initial radiographic response to RT included 2 complete responses (CR), 2 partial responses (PR), 4 stable disease, 3 progressive disease (PD). Two patients were classified as PD due to the development of distant metastases less than 2 months after completing RT. Two grade 3 toxicities were documented (one early, one late). At a median follow-up of 30.4 months, three patients had died with evidence of PD, two had died without evidence of PD, three were alive with metastases, and three were alive without evidence of disease progression (1 stable, 1 PR, 1 CR). From the start of RT, median overall survival was 32.1 months; progression free survival was 14.6 months. Conclusions: RT may have the potential to convert PNTs from locally-advanced to resectable. RT may also increase local control of PNTs. Consideration should be given to the use of RT in prospective trials of PNT treatment.
Predictors of positive test results in patients with cancer undergoing hepatitis B screening before chemotherapy.
Authors: Jessica Hwang, Anna S.F. Lok, Scott B. Cantor, Michael Fisch, Andrea G. Barbo, Heather Y. Lin, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2014)

143 Background: Optimal hepatitis B virus (HBV) screening strategies for patients with cancer awaiting chemotherapy are unknown. We aimed to identify predictors of HBV infection in a large cohort of patients with cancer who were systematically screened for HBV before chemotherapy. Methods: In this prospective observational study, patients with cancer at MD Anderson Cancer Center awaiting first administration of chemotherapy in an outpatient chemotherapy unit were identified and approached for HBV screening. Enrolled patients completed a CDC risk survey and had blood tests to screen for HBV (HBsAg, anti-HBc) and hepatitis C virus (anti-HCV) infection. We developed a logistic regression model to identify clinical predictors of either chronic (HBsAg+/anti-HBc+) or past (HBsAg-/anti-HBc+) HBV infection. Model fit was assessed using the Hosmer-Lemeshow goodness-of-fit test. We present results from year 1 of our ongoing 2-year study. Results: From July 2013 to June 2014, 1176 patients (mean [SD] age, 58 [13] years) have completed the risk survey and HBV screening. Of these, 54% were women, 84% white, 9% black, 4% Asian, and nearly 11% Hispanic. Over 20% had a hematologic malignancy, 1% liver cancer, and 77% a solid tumor other than liver cancer. Almost 12% of patients were born outside the US. Three patients (0.26%) had chronic and 84 (7%) had past HBV infection. Among the latter, 9 patients were also anti-HCV+. Predictors (odds ratio [OR]; 95% CI) of having either HBsAg+ or anti-HBc+ result included black race (4; 2-7), Asian race (4; 2-9), birthplace outside the US (5; 3-10), and having lived with someone with HBV (3; 2-7). Patients who reported ever injecting drugs (OR 7; 2-24) or being a man currently having sex with another man (OR 42; 6-277), or who were anti-HCV+ (OR 5; 1-16) had high risk of HBsAg+ or anti-HBc+ result. Conclusions: Known HBV risk factors are predictive of chronic or past HBV infection in patients with cancer. These results can assist in the development and testing of risk-based screening strategies to enhance accurate and cost-effective identification of patients with HBV infection.
Association of CD44s and CD44v6 expression with survival outcomes in malignant fibrious histiocytoma.
Authors: Matthias Peiper, Edwin Boelke, Christiane Matuschek, Nikolas H. Stoecklein, Christopher Poremba, Matthias Schauer, Wolfram Trudo Knoefel
Journal: Journal of Clinical Oncology (2012)

44 Background: New prognostic markers are being searched to determine the value of adjuvant and/or palliative treatment in soft tissue sarcomas (STS). Several studies showed that CD44 expression was associated with a better outcome in certain cancers, such as bladder tumors. The aim of this study was to evaluate the expression of CD44 in STS of the adult and to determine whether this correlates with the clinical outcome. Methods: We examined the clinical outcome of 34 adult MFH patients (19 males and 15 females, average age 62 years, median 63 years, ranged from 38 to 88 years) who underwent curative treatment The majority of patients received adjuvant radiotherapy (n = 25). No patients received initial adjuvant chemotherapy. The prognostic value of CD44s and isoform expression were evaluated by immunohistochemistry of tissue microarrays. Results: At first, we split the data for each variant of CD44 into two equally sized groups at the medians to the expression values (low and high). We apply a log rank test on the two groups and use the p value as an evaluation criterion for the usefulness of the grouping. CD44s and CD44v6 expression significantly correlated with an improved outcome whereas CD44v8 and h CD44 were not significant. Conclusions: CD44s and CD44v6 expression seem to be associated with improved survival in malignant fibrous histiocytoma.