tbuckley/cabot-search huggingface dataset:
Comparison of cytarabine, mitoxantrone, and CNDAC in vitro treatment of AML bone marrow and peripheral blood cells.
Authors: S. Jagan, L. A. Paganessi, S. Gezer, A. Rizman, D. Rifai, M. C. Keller, M. L. Larson, P. Venugopal, S. Frame, K. W. Christopherson
Journal: Journal of Clinical Oncology (2011)

6588 Background: A major challenge in developing treatment regimens for AML is identifying strategies to prevent disease relapse. Advances in understanding the biology of AML leukemogenesis have revealed that schedule and combination strategies for treatment influence outcome. This study examines the in vitro effect of current chemotherapeutic drugs cytarabine, mitoxantrone (synthetic anthracynedione) and the active form of oral drug sapacitabine, 2’-C-Cyano-2’-deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC) on leukemic cells from 5 AML patients. Methods: Untreated AML bone marrow (BM) and peripheral blood (PB) mononuclear cells (MNC) from 5 patients were treated with Ara-C (1-100μM), CNDAC (1-100μM) and Mitoxantrone (0.005 – 0.5μM) for 4 days. Total WBC counts ranged from 27.06 – 93.05 K/µL with 58 – 99% CD34+ cells. BM MNC’s were exposed to drugs in a co-culture system using the mouse stromal cell line, M2-10B4. PB MNC’s were drug treated in suspension. Post treatment, both BM and PB cells were replated on M2-10B4 stromal layers. Non-adherent cells were assessed for overall viability post-treatment and at 3, 7 and 31 days of culture following drug treatment. Results: In the PB, after 3 days post drug removal, the total cell survival was significantly lower for cells treated with 1µM CNDAC or 0.005µM Mitoxantrone compared to 1µM cytarabine (p<0.05, n=5). Although a similar trend was seen with BM cells, it did not reach significance. In both the BM and PB, survival of cells treated with 1µM CNDAC or 0.005µM mitoxantrone over the 35 day culture period was significantly less than untreated cells (p<0.05, n=5). The survival of 1µM cytarabine treated cells was not significantly lower. Conclusions: CNDAC and mitoxantrone have a longer in vitro impact on the survival of PB cells than cytarabine. A subset of similar cells in the BM was most likely protected by the stroma in the BM co-culture system, thus lessening the impact. However, as seen by the similar profiles in PB and BM, both CNDAC and mitoxantrone appear to have a greater overall effect on cell survival than cytarabine. Due to the effectiveness and ease of administration of CNDAC, it may complement cytarabine and mitoxantrone and influence optimal scheduling in treatment of AML.
Use of gene expression profiling to determine prognosis and therapeutic targets for patients with appendiceal carcinoma.
Authors: M. K. Kim, D. G. Blazer, J. H. Stewart, C. Guy, P. Shen, E. Levine, S. D. Hsu
Journal: Journal of Clinical Oncology (2011)

418 Background: Appendiceal carcinomas are rare neoplasms that often present as peritoneal surface malignancies. The tumors are treated similarly to primary colorectal metastases, despite having different biological environments. The aim of this study is to utilize genomic analyses to understand the underlying biology of appendiceal carcinoma in order to better guide prognosis and therapy. Methods: Forty-one metastatic human tumors to the peritoneum (26 appendiceal carcinoma, 15 colorectal carcinoma) were subjected to global gene expression analysis. Unsupervised hierarchical clustering was used to differentiate phenotypes based on differential gene expression. Phenotypes were further analyzed to find differences in oncogenic pathway deregulation and findings were validated using gene specific inhibitors in vitro. Results: Unsupervised hierarchical clustering revealed three distinct phenotypes, two consisting of predominantly low grade appendiceal samples (Cluster 1 and Cluster 2) and one consisting of predominantly colorectal samples (Cluster 3). Cluster 1 consisted of patients with good prognosis and Cluster 2 consisted of patients with poor prognosis (p = 0.046). Further characterization of Cluster 1 and Cluster 2 with oncogenic pathway signatures identified increased deregulation of the EGFR pathway in the poor prognosis cluster. Similarly, colon cancer cell lines with the poor prognosis phenotype were found to be more sensitive to gefitinib (EGFR inhibitor) (p = 0.038). Conclusions: The use of geneexpression profiling can be used to identify prognosis and novel therapeutic targets for patients with appendiceal carcinoma. These methods can serve as models to understand the biology of appendiceal carcinoma and to assist in the design of future trials for patients with appendiceal cancer. No significant financial relationships to disclose.
Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature
Authors: Yvonne M. Ende-Verhaar, Suzanne C. Cannegieter, Anton Vonk Noordegraaf, Marion Delcroix, Piotr Pruszczyk, Albert T.A. Mairuhu, Menno V. Huisman, Frederikus A. Klok
Journal: European Respiratory Journal (2017)

The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is relevant for management decisions but is currently unknown. We performed a meta-analysis of studies including consecutive PE patients followed for CTEPH. Study cohorts were predefined as “all comers”, “survivors” or “survivors without major comorbidities”. CTEPH incidences were calculated using random effects models. We selected 16 studies totalling 4047 PE patients who were mostly followed up for &gt;2-years. In 1186 all comers (two studies), the pooled CTEPH incidence was 0.56% (95% CI 0.1–1.0). In 999 survivors (four studies) CTEPH incidence was 3.2% (95% CI 2.0–4.4). In 1775 survivors without major comorbidities (nine studies), CTEPH incidence was 2.8% (95% CI 1.5–4.1). Both recurrent venous thromboembolism and unprovoked PE were significantly associated with a higher risk of CTEPH, with odds ratios of 3.2 (95% CI 1.7–5.9) and 4.1 (95% CI 2.1–8.2) respectively. The pooled CTEPH incidence in 12 studies that did not use right heart catheterisation as the diagnostic standard was 6.3% (95% CI 4.1–8.4). The 0.56% incidence in the all-comer group probably provides the best reflection of the incidence of CTEPH after PE on the population level. The ∼3% incidences in the survivor categories may be more relevant for daily clinical practice. Studies that assessed CTEPH diagnosis by tests other than right heart catheterisation provide overestimated CTEPH incidences.
Single-agent lenalidomide for newly diagnosed myeloma with on-demand dexamethasone: A phase II trial.
Authors: F. Buadi, M. Lacy, A. Dispenzieri, B. LaPlant, K. M. Laumann, G. S. Nowakowski, S. R. Hayman, K. Detweiler Short, D. Dingli, M. A. Gertz, P. R. Greipp, J. A. Lust, T. E. Witzig, S. R. Zeldenrust, S. J. Russell, V. Rajkumar, S. Kumar
Journal: Journal of Clinical Oncology (2011)

8080 Background: Lenalidomide (Len)-dexamethasone (Dex) combination is an effective initial therapy for multiple myeloma (MM). Len is an immunomodulatory drug and use of dexamethasone can potentially impair this effect. So we designed a trial of single agent Len, with Dex added based on response. Methods: Patients (Pts) with previously untreated, symptomatic MM with measurable disease were enrolled. Treatment consisted of Len (25 mg daily) for 3 weeks during a 4 week-cycle. Dex was added at 10 mg weekly if a partial response (PR) was not seen after 3 cycles, with dose increased by 10 mg weekly every cycle until a PR was seen or a maximum of 40 mg weekly was reached. Dex 40 mg weekly was added at any time if there was disease progression. Results: Thirty-eight pts with a median age of 66 (45-78) years; 21 (55%) females, were enrolled between Dec 2008 and Apr 2010. Twelve (34%) patients were ISS stage 3, and 9 (24%) were considered high-risk by mSMART criteria. Fifteen patients remain on study, with the majority of patients going off study for progression or alternative therapy including transplant. Overall, 26 (68%) patients had dexamethasone added to their treatment with a median time to dexamethasone addition of 3.3 months. Across the trial, 383 cycles of lenalidomide were administered, 205 (53%) with dexamethasone as well. Hematological toxicity was the main adverse event observed, with 45% of patients with a grade 3 or 4 event at least possible related to therapy. Fatigue was the most common non-hematological toxicity. The three-cycle response rate (>PR, without Dex) was 29%. The overall confirmed response (>PR) rate, including those with Dex added per protocol, was 58% (21% VGPR or better). Median time to response of 3.7 months. There have been 11 disease progressions, 8 of which occurred on study. The one-year estimated overall survival is 91%. Conclusions: Len as a single agent with Dex added based on response is a feasible strategy that will allow avoidance of dexamethasone related side effects, especially in patients where other coexisting illnesses make steroid side effects difficult to manage. The responses are slower than seen with Len and Dex and neutropenia and fatigue are the main toxicities.
Guideline adherence for diagnosis of liver cancer in veterans.
Authors: Yvonne Sada, Eric David, Hashem El-Serag, Hardeep Singh, Jessica Davila
Journal: Journal of Clinical Oncology (2013)

89 Background: The incidence of hepatocellular cancer (HCC) is rising. Practice guidelines provide the recommended approach for HCC diagnosis, but adherence to diagnostic guidelines is unknown. Methods: In a national sample of veterans with confirmed HCC, we performed a retrospective chart review of patients with cirrhosis and a new liver mass on imaging between 2005 and 2011. Clinical data was used to assess adherence to American Association for the Study of Liver Diseases guidelines. Patients with inadequate data to assess guideline adherence (missing liver mass size, imaging technique, or diagnostic report) were excluded. We identified factors that contributed to guideline non-adherence. Initial liver mass date was the first date a liver mass was reported on imaging (CT, MRI, or ultrasound). Gold standard test date was the date a diagnosis of HCC could have been made by guideline recommended testing and criteria. Diagnosis date was the date a provider documented the diagnosis. Results: We reviewed charts for 380 patients. Overutilization of diagnostic tests after a gold standard test occurred in 112 patients (31%), and 17 (4%) had insufficient tests. Guidelines were not followed in 124 (33%). Of these 124, 68 (55%) had liver masses that increased in size during diagnostic work-up. The most common factors associated with guideline non-adherence were unnecessary testing such as biopsy after a gold standard image (43%) and the presence of a contraindication to a guideline recommended image or biopsy (12%). Patient factors (missed appointments, declining work-up) accounted for only 3% of cases. Median time between the initial liver mass and gold standard test was 15 days (IQR: 0-99). Median time between the initial liver mass and diagnosis was 50 days (IQR: 12-191). Most diagnoses were made by gastroenterology (51%), followed by primary care (19%), and oncology (10%). Conclusions: One-third of patients with HCC were not diagnosed based on guidelines. These concerns include confidence in diagnosis (lack of recognizing HCC diagnosis despite gold standard evidence) and over testing, which both lead to diagnostic delay. Our findings warrant further evaluation of contributory factors to develop interventions that improve the diagnostic process for HCC.
Salivary gland tumors as secondary malignancies after treatment for pediatric bone sarcoma.
Authors: J. Kreshak, C. Ferrari, G. Bacci, M. Gambarotti, S. Ferrari, M. Mercuri, A. Longhi
Journal: Journal of Clinical Oncology (2011)

e19666 Background: Osteosarcoma and Ewing’s sarcoma are bone sarcomas that primarily affect children and young adults. The advent of chemotherapy greatly improved long term survival rates, however, they have been found to have high rates of secondary malignant neoplasms, likely due to aggressive multimodality treatment and radiation therapy. The most frequent second malignancies noted in the literature are CNS tumors, breast cancer, leukemia, and sarcomas. Salivary gland tumors are rare as primaries; their incidence rises in the setting of prior cancer treatment. The objective of this retrospective study was to evaluate secondary salivary gland malignancies in patients previously treated for pediatric bone sarcomas in a single institution. Methods: We analyzed our database of 1376 patients treated for osteosarcoma or Ewing’s sarcoma at a single institution from 1983–2008. Of 39 secondary malignancies found, 6 were salivary gland tumors. These charts were retrospectively reviewed for histology, respective dates, and treatment protocols. Results: Of 1376 patients, 883 were treated for osteosarcoma, 493 for Ewing’s sarcoma. 39 secondary malignancies were found (2.8%); 6 of these were salivary gland tumors (15.3%) (4 after treatment for osteosarcoma, 2 after Ewing’s sarcoma). Median patient age was 13 years (10-27); all were treated with chemotherapy, none with head or neck radiation. Median interval between the two diagnoses was 65 months (48-97). 5 salivary gland tumors were mucoepidermoid carcinoma of the parotid gland and 1 was acinic cell carcinoma of a submandibular gland. 4 tumors were low grade, 1 intermediate grade, 1 high grade. All were treated with surgery alone; all patients were free of both diseases at last follow-up (median follow-up post diagnosis of secondary malignancy: 57 months; range 18-179). Conclusions: In our series, secondary salivary gland cancers in patients previously treated for bone sarcomas were seen at a higher rate than is observed for these cancers as primaries and were unusually frequent relative to other forms of secondary malignancy (third most common). In young patients previously treated with chemotherapy, painless swelling of a salivary gland should always be considered suspicious.
Trends in cytoreductive nephrectomy in the eras of immuno and targeted therapy.
Authors: Brian J. Minnillo, Hui Zhu, Matthew J. Maurice, Robert Abouassaly
Journal: Journal of Clinical Oncology (2014)

472 Background: Since the publication of randomized studies demonstrating a survival advantage in patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy, cytoreductive nephrectomy (CN) has played an integral role in the management of these patients. Our objective is to describe the use of CN in the eras of immuno and targeted therapy for mRCC. Methods: Using the National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, we identified patients with histologically confirmed mRCC. We examined patient, provider and disease factors associated with CN. We also assessed short-term surgical outcomes of CN. A multivariable logistic regression was used to evaluate factors associated with CN. Results: From 1998 to 2011, 30.1%(17,714) of the 58,810 patients with mRCC underwent CN (Table). Over this timeframe, there was a gradual increase in the proportion undergoing surgery (17.3% to 35.7%). In those who underwent CN, the mean length-of-stay (LOS) was 6.1 days. The 30-day readmission rate and 30-day mortality were 5.6% and 3.8%, respectively. On multivariate analysis, patients who were treated at an academic facility (OR 1.94, 95% CI 1.79-2.11, p &lt;.0001) were more likely to be treated with CN. After adjusting for covariates, patients of African American race (OR 0.52, 95% CI 0.48-0.56, p &lt;.0001), a tumor size of &gt;14cm (OR 0.57, 95%CI 0.52-0.62, p&lt;.0001), or a Charlson/Deyo score of ≥ 2 (OR 0.62, 95% CI 0.57-0.68, p &lt; .0001) were less likely to be treated surgically. Conclusions: Cytoreductive nephrectomy for mRCC appears to be steadily increasing over time, particularly in academic medical centers, even after adjusting for potential confounders. Despite this population’s advanced disease, LOS, 30-day readmission rate and 30-day mortality are relatively low. Our results suggest that CN utilization remains high in the era of targeted therapy. [Table: see text]
Colorectal signet-ring cell carcinoma: Responsive to adjuvant chemotherapy but still a poor prognosis.
Authors: Niek Hugen, Rob H. A. Verhoeven, Valery E. P. P. Lemmens, Carola J. C. Van Aart, Marloes A. G. Elferink, Johannes H. W. de Wilt, Iris D. Nagtegaal
Journal: Journal of Clinical Oncology (2014)

529 Background: Colorectal signet-ring cell carcinoma (SRCC) has been associated with a poor survival compared to mucinous adenocarcinoma (MC) and the common adenocarcinoma (AC). Prognostic impact of tumor localization is unknown and efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyses prognostic impact of SRCC and determines whether SRCC patients benefit from adjuvant chemotherapy for colon cancer equally compared with AC. Methods: Data on 196,757 patients with CRC in the Netherlands in the period 1989 and 2010 was included in this nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. Results: SRCC was found in 1.0% of CRC patients. SRCC patients presented more frequently with stage III or IV disease than AC (75.2% versus 43.6%, P&lt;0.0001) and SRCC was more frequently found in the proximal colon (57.7% versus 32.0%, P&lt;0.0001). SRCC patients had a poor 5-year relative survival of 31% in colon and 20% in the rectum compared to 57% and 59% in AC (P&lt;0.0001). This poorer survival for SRCC was found in stage II, III and IV. In comparison with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. Conclusions: Prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but colonic SRCC patients seem to benefit from adjuvant chemotherapy equally compared with AC. Reduced efficacy of adjuvant chemotherapy therefore does not seem to explain the poor outcome in SRCC patients. We recommend to adhere to adjuvant treatment guidelines for all histological subtypes, but encourage clinical trials to take histological subtype into account for stratification.
Small caliber covered self expanding metal stents in the management of malignant dysphagia.
Authors: Steven Kucera, Ravi Shridhar, Jason Klapman, Cynthia L. Harris, Sarah E. Hoffe, James S. Barthel, Khaldoun Almhanna, Kenneth Meredith
Journal: Journal of Clinical Oncology (2016)

151 Background: Use of large caliber ( ≥ 18 mm body diameter) self expanding metal stents (SEMS) for management of malignant dysphasia is associated with substantial adverse event (AE) and mortality rates (MRs). We sought to determine dysphagia response, stent migration rates, and AE and MRs, for small caliber covered SEMS (sccSEMS) with body diameters (BDs) between 10 - 16 mm in malignant dysphagia. Methods: We identified 31 patients underwent direct endoscopic placement of 50 sccSEMS. Patients were monitored for change in dysphagia score (DS), stent migration, AEs, and death. Results: The cohort consisted of 23 (74%) men and 8 (26%) women with a median age of 64 years (35 - 87 years). Esophageal adenocarcinoma (AC) was present in 19 (61%) patients and squamous cell carcinoma (SCCA) in 12 (39%) patients. Of the patients with SCCA, 2 tumors were located in the proximal esophagus, 7 in the mid-esophagus and 3 in the distal esophagus. All 19 ACs were located in the distal esophagus. The AJCC clinical stages at time of sccSEMS placement were: 1 (3%) Stage II, 8 (26%) Stage III, and 22 (71%) Stage IV. The initial pre-stent lumen diameter was less than 8 mm in 77% (24/31) of patients. The initial pre-stent lumen diameter was equal to 9 mm in 1 patient (3%), equal to 10 mm in 4 patients (13%), and equal to 11 mm in 2 patients (6%). The median pre-stent tumor length was 5.0 cm (interquartile range 4.0 – 7.0 cm). Dysphagia score improved in 30 of 31 patients (97%). The median DS decreased from 3 to 2 (p &lt; 0.0001). The median effective duration of first sccSEMS placement was 116 (95% CI: 75-196) days. Major and minor AE rates were 6.5% and 19.4% respectively. No stent related deaths were encountered. The overall migration rate was 36% (18/50). The anticipated migration rate was 45.7% (16/35) and the unanticipated migration rate was 13.3% (2/15) (p = 0.052). Positive effective clinical outcome occurred in 93.5% (29/31) of cases. Conclusions: In malignant dysphagia, direct endoscopic sccSEMS placement provided acceptable dysphagia control and migration rates with substantial reductions in stent related AEs and MRs compared to those reported for large caliber SEMS.
Eleven-year experience with a web-based medication occurrence (MO) reporting tool in a community oncology practice.
Authors: J. Russell Hoverman, Tae W Jang, Jim R. Schwartz
Journal: Journal of Clinical Oncology (2016)

53 Background: At ASCO 2007, we presented 2 year experience with a web-based Medication Occurrence (MO) reporting tool. We now report the 11 year experience in a single outpatient oncology practice. Methods: Since December 2003, Texas Oncology (TxO) sites have entered information on Medication Occurrence (MO) reports in an electronic Variance Reporting tool. The pharmacy management team generates reports monthly for the Texas Oncology Quality Oversight Committee and each site Quality Committee for analysis and follow-up action. The data are analyzed according to a pre-set group of parameters (retail vs. clinic, near miss vs. actual occurrence, severity level 1-8, categories of occurrence). Recently these data were analyzed for the years 2004-2014 to assess trends in MOs. Results: Over 11 years there were 2,163,249 transactions for a chemotherapy infusion or injection. There were 10845 MOs of which 5,143 were adverse drug reactions (ADRs). Near misses accounted for 16.7% of unadjusted MO rate and 31.8% when ADRs were excluded. MO rate with ADR was 0.46%, without ADR 0.24%. Retail MO rate was 0.02% on 1,771,148 transactions. Rituximab was 20.9% and paclitaxel 16.4% of ADRs. Tying reporting to clinic performance increased reporting by site and number of sites. EHR related MOs and Near Misses were each reported as MOs and artificially inflate numbers due to double counting. There were 10 deaths over 11 years. With these data, we were able to 1) Promote an epinephrine protocol for severe drug reactions, 2) Obviate the need for AEDs at every site, 3) Find no difference in rituximab reactions by geographic region, 4) Make assessments regarding cost and toxicity of iron compounds, 5) Target specific drugs for ADR risk. 6) Assess prophylactic corticosteroid regimens in taxane administration. Conclusions: Web-based reporting in the outpatient community setting is feasible and identified many topics for quality improvement initiatives. The importance of double-checking and a culture of safety is reinforced by the number of avoided MOs indicated by the near miss percentage.