tbuckley/cabot-search huggingface dataset:
Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer.
Authors: Jae J. Kim
Journal: Journal of Clinical Oncology (2016)

87 Background: To suggest an appropriate surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancers, based on incidence and patterns of local, metachronous, and extragastric recurrence. Methods: Between 2003 and 2011, 1497 consecutive patients with 1539 differentiated-type early gastric cancers meeting absolute or expanded indication criteria underwent curative ESD. They were followed up with esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) under a standardized surveillance protocol. Long-term outcomes were analyzed for 1306 patients with at least 1 year’s follow-up. Results: Incidences of residual and synchronous lesions detected within 1 year were 0.13 % and 0.87 %, respectively. During median 47 months of follow-up, there was 1 local recurrence (0.08 %; early gastric cancer) and 47 cases of metachronous recurrence (3.6 %; 44 early gastric cancers, 3 pT2 advanced gastric cancers); all were curatively treated. During a 5-year surveillance, the cumulative incidence curve of metachronous recurrence increased linearly. Median time from ESD to metachronous recurrence was 30 months. There were 2 extragastric recurrences (0.15 %) in lymph nodes, at 5 and 4 years, respectively, after curative ESD for absolute and expanded indications. The patient with the expanded indications underwent a palliative operation and died of gastric cancer progression. Conclusions: There was a constant incidence rate of metachronous recurrence during a 5-year surveillance period and there was extragastric recurrence at least 4 years after ESD of early gastric cancer even for absolute indications. Therefore, annual or biannual surveillance EGD and abdominal CT might be necessary for at least 5 years after curative ESD for early gastric cancers, with absolute as well as expanded indications.
Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and myocardial dysfunction.
Authors: Giovanni Mantovani, Mariele Dessi', Alessandra Piras, Clelia Madeddu, Laura Orgiano, Christian Cadeddu, Giorgia Antoni, Giuseppe Mercuro
Journal: Journal of Clinical Oncology (2012)

9006 Background: Chronic inflammation, oxidative stress and renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, reduces anthracycline (ANT)-induced CTX. Methods: A phase II placebo (PLA)-controlled randomized trial was carried out to assess the role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were assessed. All assessments were carried out at baseline, after every 100 mg/m 2 EPI dose and at 6, 12 and 18-month follow-up (FU). Results: A significant reduction in the SR peak in both arms was observed at t 2 (cumulative dose of 200 mg/m 2 EPI) in comparison to t 0 . Conversely, at t 3 , t 4 (300, 400 mg/m 2 EPI), 6, 12 and 18-month FU, the SR increased reaching the normal range only in TEL arm, while in PLA arm SR remained significantly lower as compared to t 0 . The differences between SR changes in PLA and TEL arms were significant from 300 mg/m 2 EPI (t 3 ) up to 18 month-FU. IL-6 increased significantly in PLA arm at t 2 compared to t 0 , but remained unchanged in the TEL arm. ROS levels also increased significantly at t 2 vs. baseline in PLA arm, while remained unchanged in TEL arm. The mean change in ROS and IL-6 at t 2 was significantly different between the two arms. At 3, 6, 12 and 18 month-FU, ROS and IL-6 decreased in comparison to t 2 in PLA arm, while remained low in TEL arm. Conclusions: Our results suggest that TEL is able to reverse acute EPI-induced myocardial dysfunction and maintain a normal systolic function up to 18 month-FU. These effects are likely due to two different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.
Monitoring response and treatment outcome in patients with chronic phase chronic myeloid leukemia (CML) treated with imatinib.
Authors: A. Teitelbaum, D. Spencer, V. K. Bollu, B. Chastek, J. Coombs, M. Kulakodlu, R. Morlock
Journal: Journal of Clinical Oncology (2011)

e16612 Background: For patients with chronic myeloid leukemia (CML) who achieve major molecular response (MMolR), long-term disease-free survival is possible, as well as a lower risk and incidence of relapse. For this reason, molecular testing has become an important tool in assessing CML prognosis. This study examined the frequency of cytogenetic and molecular testing and treatment response among CML patients newly treated with imatinib. Methods: Adult patients diagnosed with CML, newly treated with imatinib, and continuously treated with imatinib or another tyrosine kinase inhibitor (TKI) for at least 6 months were identified between May 2001 and 31 January 2009 from a large US commercial insurance claims database. Patients were required to be enrolled in the health plan for at least 90 days prior to and at least 180 days following the index date. Patients with baseline use of a TKI or who were not in chronic phase at initial diagnosis were excluded from the study. For each patient, the medical chart was requested from a treating physician and was reviewed to determine frequency of testing and the corresponding response (based on lab tests and/or physician notation). Results: Overall, 442 patients with CML were identified in the claims database, with chart data available for 125 patients. Mean (SD) age was 52 (11) years, 61% were male, and the median length of follow-up was 599 days. 104 (83%) had at least 1 conventional or FISH cytogenetic test and an additional 4 patients had a physician’s note. 76 (61%) had at least 1 quantitative polymerase chain reaction (PCR) test performed during the follow-up. The average number of tests per year was 1.9 (1.3) for cytogenetic/FISH tests and 1.9 (1.2) for PCR tests. 75 (73%) of 103 patients with cytogenetic data experienced complete cytogenetic response at some point and 9 (8.7%) had a loss of response. 66 (79%) of 84 patients with molecular data achieved MMolR, and 12(14%) had a loss of response. Conclusions: In this study, a large proportion of patients were untested or under tested relative to NCCN guideline recommendations. Patient charts were frequently incomplete and often lacked a large amount of data.
Characteristics of treatment-related dermatological toxicity in colorectal carcinoma.
Authors: A. M. O'Reilly, B. R. Bird, J. O' Keeffe
Journal: Journal of Clinical Oncology (2011)

617 Background: The use of novel targeted therapies is becoming increasingly prevalent. This study aimed to determine how novel- targeted therapies have changed the profile of dermatological toxicity in patients being treated for colorectal carcinoma. Methods: Retrospective analysis was performed in a single institution for all patients presenting over a period of 4 weeks. Participants were followed up for the remainder of the study period. Patient charts were reviewed for previou incidences of dermatological toxicity. Toxicity was graded using the Common Toxicity Criteria version 3. Statistical analysis was performed using SPSS version 19. Results: A total of 45 patients receiving treatment for colorectal carcinoma were included in the final analyses. Twenty-nine of these received novel targeted therapy (NTT) including bevacizumab, cetuximab, capecitabine, and panitumumab. Sixteen participants received traditional chemotherapy. In total 79 toxicities were evaluated. Participants receiving NTT experienced a higher mean number of toxicities (2.2 [95%CI 1.9-3.7]) then those receiving traditional chemotherapy (0.9 [95%CI 0.6-1.2]), p &lt; 0.01. Those receiving NTT experienced significantly more HFS (p &lt; 0.01) and rash (p &lt; 0.01) Participants receiving NTT experienced significantly more grade 2 or above dermatological toxicity (p &lt; 0.01) Those receiving NTT underwent more alterations in chemotherapy then those receiving traditional chemotherapy (p &lt; 0.05). HFS affected 14 (31%) participants, 4 of these were grade 2 or above. Twenty (44%) participants experienced rash, 4 of these were grade 2 or above. All patients (9) receiving cetuximab experienced acneiform rash, 3 were grade 2 or above, 5 patients required dose reduction/dose delay. Fifteen (33%) participants experienced stomatitis. Additional toxicities evaluated include alopecia (13%), nail dystrophy, and xerosis. Conclusions: Those receiving novel targeted therapy for the treatment of colorectal carcinoma may be at increased risk of developing dermatological toxicity. Dermatological toxicity in this group may be of higher grade and greater complexity. Treatment of dermatological toxicity in this group may require more dose modifications. No significant financial relationships to disclose.
Clinical and immunologic impact of short course enzalutamide without androgen deprivation therapy for biochemically recurrent prostate cancer.
Authors: Ravi Amrit Madan, Renee Nicole Donahue, Harpreet Singh, Fatima Karzai, Marc Robert Theoret, Christopher Ryan Heery, Julius Strauss, Nancy Harold, Anna Couvillon, Jennifer L. Marte, Amy Hankin, Italia Grenga, Guinevere Chun, Inger L. Rosner, David G. McLeod, Lisa M Cordes, William Douglas Figg, William L. Dahut, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2016)

214 Background: Enzalutamide (enz) is FDA approved for advanced prostate cancer, but studies are evaluating enz in earlier stages of disease. We have conducted a clinical trial (NCT01875250) of enz ± a therapeutic vaccine in biochemically recurrent prostate cancer. Methods: Eligible patients (pts) had a PSA between 2.0-20.0 ng/ml, no metastatic disease and normal testosterone (T). Treatment for all pts included enz 160 mg daily for 84 days (D), but no T lowering therapy was permitted. This analysis evaluated all pts for the impact of enz on PSA and T regardless of randomization. Pts treated with Enz alone were evaluated for immune responses.The impact of the vaccine will be evaluated after protocol-defined requisite follow-up. Results: Median age for all pts (n = 34) was 66 years (range: 52-87), with a median on-study baseline PSA of 4.55 ng/ml (2.02-19.43). Common adverse events included fatigue and breast tenderness, but no pts discontinued enz for toxicity. The median PSA decline was 99% (range: 52% to &gt; 99%) with 11/34 pts having undetectable nadirs. Median time to first PSA rise after 84 D course of enz was 29 D (13-70) and median recovery to baseline PSA in 25 evaluable pts was 190 D (84-469). T increased above normal limits in 18/34 pts (median Tmax = 802 ng/dl). Immune analysis (n = 12) indicated enz alone increased naïve T-cells and NK cells, and decreased several subsets of myeloid derived suppressor cells with a highly suppressive phenotype. Conclusions: The preliminary findings from this study suggest that short-course enz is well tolerated, leads to prolonged PSA suppression and enhanced immune responses in patients with biochemically recurrent prostate cancer. These immune studies provide the rationale for the use of enz in combination with immunotherapeutics in this and other malignancies. Clinical trial information: NCT01875250.
A randomized trial of PSA-peptide based, specific active immunotherapy in HLA-A2+ patients with prostate cancer: Comparison of two different vaccination strategies
Authors: S. Hallmeyer, S. Perambakam, S. Reddy, N. Mahmud, J. Sosman, P. David
Journal: Journal of Clinical Oncology (2005)

2519 Background: Standard treatments for prostate cancer (Pca) cause undesirable side-effects and often fail. Specific T cell immunotherapy against defined Pca-associated antigens offers the potential for less toxic, more effective outcomes. Methods: A pilot trial was conducted to determine whether PSA 146–154 peptide vaccination can induce specific T cell immunity without associated toxicity. The trial compared two different vaccination methods. Arm1-PSA peptide and GM-CSF injected i.d. versus Arm 2-PSA peptide-pulsed, autologous dendritic cells infused i.v. Two groups of HLA-A2+ patients [Group A (n=14): high-risk, local disease; Group B (n=14): metastatic, hormone-sensitive disease in remission] were randomized 1:1 to the two treatment arms. Patients were vaccinated on weeks 1, 4, and 10. Immune responses were monitored by delayed-type hypersensitivity (DTH) skin testing and in vitro T cell assays on weeks 4, 14, 26, and 52. Tumor status was monitored by serial PSA levels and clinical tests. Results: Vaccinations were completed in April of 2004. The majority of patients have completed 52 weeks of observation. Both vaccination methods have been well tolerated with no grade 3/4 toxicities. Fourteen patients (9 on Arm 1 and 5 on Arm 2) have developed specific DTH responses to PSA 146–154 peptide. Eleven DTH responders (78%) have had stable or declining serum PSA levels. Nine DTH non-responders (64%) have had rising PSA levels and/or clinical progression. Both vaccination methods elicited specific T cell responses per cytokine release and tetramer assays. Conclusion: Vaccination of HLA-A2+ patients with PSA146–154 peptide is well tolerated and elicits specific T cell immunity. Intradermal administration of PSA 146–154 peptide with GM-CSF and intravenous administration of PSA 146–154 peptide-pulsed dendritic cells are both effective immunization strategies. Induction of specific T cell immunity to PSA 146–154 peptide in patients with Pca correlates with less disease progression. No significant financial relationships to disclose.
Phase I, dose-finding study of monotherapy with AZD8931, an inhibitor of ErbB1, 2, and 3 signaling, in patients (pts) with advanced solid tumors.
Authors: U. Keilholz, V. Moiseyenko, A. Makhson, V. Semiglazov, M. Learoyd, A. Saunders, M. Stuart, S. Tjulandin
Journal: Journal of Clinical Oncology (2011)

3097 Background: AZD8931 is an oral, equipotent inhibitor of ErbB1, ErbB2 and ErbB3 receptor signaling. Methods: This open-label, multiple ascending (standard 3+3 design) dose cohort study (NCT00637039) determined the safety, tolerability, and PK of AZD8931. Pts received a single oral dose of AZD8931 followed by a 4-day observation and then AZD8931 bid for 21 consecutive days (continuation post day 21 was optional). Results: 28 pts (mean age 56 years) received AZD8931 (n=5, 40 mg bid; n=8, 80 mg bid; n=6, 160 mg bid; n=6, 240 mg bid; n=3, 300 mg bid); 21 had metastatic disease and 27 had received prior cancer therapy. The most common primary tumors were ovary (n=8) and breast (n=5). The 21-day repeat-dosing period was completed by 22 pts and 9 remained on treatment after this period. Median duration of exposure to AZD8931 was 22 days (range 7–140). DLTs were identified in 1/6 pts in the 240 mg bid cohort (Grade [Gr] 3 rash) and in 2/2 evaluable pts in the 300 mg bid cohort (Gr 3 and Gr 4 diarrhea). Skin and subcutaneous tissue disorders and GI disorders were the most common system organ class AEs. In the 40 mg bid group cohort all skin-type AEs (n=5) were mild (Gr 1). AZD8931 demonstrated rapid absorption (median tmax was 1–3 h), was well distributed, had moderate to high clearance and terminal t½ of 11 h. Following continuous bid dosing, steady state was achieved by day 2, accumulation was ~1.5-fold and no time-dependent changes in PK were observed. Exposure increased proportionally with dose up to 160 mg; for single doses >160 mg, exposure increased slightly greater than proportionally with dose. Of 21 pts evaluable for response at day 21, 12 had stable disease and 9 had disease progression. Conclusions: The MTD of AZD8931 determined from tolerability data during the DLT period was 240 mg bid. However, more long-term data are needed to define a dose of AZD8931 suitable for chronic treatment. AZD8931 dose (n) 40 mg bid (5) 80 mg bid (8) 160 mg bid (6) 240 mg bid (6) 300 mg bid (3) Total (28) Patients with an AE considered related to study treatment, n Any grade 5 8 6 6 3 28 Grade ≥3 1 3 3 4 3 14 SAE 0 0 0 0 1 1 Most frequent grade ≥3 skin-related and GI AEs, n Diarrhea 1 0 2 2 2 7 Acne-type rash 0 3 0 1 0 4 Skin exfoliation 0 1 0 1 0 2 Ascites 0 1 1 0 0 2
EGFR/AKT pathways alterations in gliomas
Authors: L. M. Núñez, A. Muggeri, E. Arias, A. L. Taratuto, G. Sevlever, B. Diez, H. Martinetto
Journal: Journal of Clinical Oncology (2008)

2061 Background: EGFR/AKT pathways anomalies are well known in gliomas. Nevertheless, specific alterations for the different types of gliomas have not been assessed. Our goal was to look for differences in the status of EGFR, 10q and CDKN2A/ARF genes in three groups of gliomas. Methods: We performed molecular analysis of 43 oligodendrogliomas (OD), 22 oligoastrocytomas (OA) and 18 glioblastomas (GBM). LOH at 1p, 19q and 10q was assessed by Real Time PCR quantitative microsatellite analysis. Markers for 10q analysis (D10S536 and D10S1683) are located proximal to PTEN and DMBT-1 loci respectively. EGFR and CDKN2A/ARF were studied by multiplex real time PCR. Clinical information related to diagnosis, tumor characteristics and outcome was also documented. Results: As expected by current knowledge, alterations in EGFR/AKT pathways were highly common in GBM, showing significant differences in EGFR amplification and also 10q and p16 deletion, when compared to OD. In a more detailed analysis, including number of copies of EGFR and specific marker deletions at 10q, we found differences not previously reported between these groups. Amplification of EGFR was present in 66% of the GBM and 7% of the OD. When copy number was considered, every OD carrying amplified EGFR had trisomy while amplification pattern in GBM showed more than 3 copies in 92% of the cases (p=0.008). When 10q was analyzed 83% of GBM and 30% of OD showed alterations. Furthermore, among tumors harboring 10q alterations, 93% of GBM showed loss of both markers, while 69% of OD only showed one marker loss (p=0.001). Partial deletions of 10q affected more commonly marker proximal to DMBT-1 (p=0.02). OA displayed an intermediate profile; depending on the marker, they were closer to OD (CDKN2A/ARF) or to GBM (10q, EGFR). Conclusions: The major use of the molecular analysis of gliomas has been focused in 1p and 19q alteration as a prognostic tool. EGFR, CDKN2A/ARF genes alterations and LOH at 10q, have also shown to be useful for characterization and management. Our study suggests that the combination and detailed analysis of these markers may also help in obtaining a more accurate classification of these tumors. No significant financial relationships to disclose.
Monitoring Patterns and Subsequent Outcomes Among Patients with Philadelphia Chromosome Positive Chronic Myeloid Leukemia (Ph+ CML) Treated with Imatinib in a Community Setting
Authors: James Jackson, Lei Chen, Kavita R Sail, Solveig G. Ericson, Sally Haislip, Joyce Sharpe, James Gilmore, Mansoor N Saleh
Journal: Blood (2012)
High-cost imaging for managed care Medicare beneficiaries with cancer, 2001-2006.
Authors: E. T. Loggers, P. A. Fishman, M. C. Hornbrook, C. C. Greenberg, M. C. O'Keeffe-Rosetti, A. Ramaprasan, N. Q. Vanneman, E. H. Wagner, J. C. Weeks, D. P. Ritzwoller
Journal: Journal of Clinical Oncology (2011)

6014 Background: Medicare expenditures are being driven upward by a rapid increase in advanced imaging in fee-for-service Medicare (FFSM) environments as part of the diagnosis and treatment of Medicare beneficiaries with cancer. Imaging rates for Medicare beneficiaries enrolled in managed care plans (MCM), where incentives may differ, are unknown. Comparing utilization in FFSM vs MCM is the first step toward comparative effectiveness evaluations of cancer imaging across economic and care models. Methods: Imaging procedures were identified for incident diagnoses of breast, colorectal (CRC), lung, prostate, leukemia, and non-Hodgkin lymphoma (NHL) cancers from 2001-2006 from 3 large managed care organizations in Washington state, Oregon, and Colorado using ICD-9-CM, CPT and HCPCS codes, consistent with methods detailed in Dinan MA, JAMA, 2010. Imaging procedures included, among others: CT scan, MRI, PET scan, and nuclear medicine studies. Two-year overall and cancer-specific mean imaging counts per MCM were calculated and compared to the previously published rates for FFSM. Results: There were 4,370 incident cancer cases, median age 79 years (interquartile range 74-83), 48% male. 41,812 total imaging procedures were performed, 25% among lung cancer patients. The mean number of images per MCM for two years of follow-up across all cancer types rose from 7.4 in 2001 to 12.9 in 2006. In 2001, rates were lower in MCM than in FFSM for all imaging modalities, including PET scans, across all cancers. By 2006 imaging rates remained lower in MCM than FFSM for the majority of modalities; exceptions included the mean number of CT scans for leukemia (4.4 vs 3.1, MCM versus FFSM respectively), NHL (7.9 vs 6.3), CRC (5.2 vs 4.8) and prostate cancer (2.5 vs 2.1). MCM rates were also higher than FFSM for nuclear medicine (1.3 vs 1.0) and PET scanning (1.3 vs 1.1) for NHL and higher for MRI for leukemia (0.6 vs 0.5). Conclusions: Overall rates of imaging are increasing for Medicare beneficiaries in managed care environments more slowly than in fee-for-service, but with greater emphasis on CT scanning and fewer PET scans on average. Future analyses will compare costs and outcomes in FFSM vs MCM, and differences in scanning rates by age (over vs under 65) in MCM.
Targeted MEK Inhibition in Patients with Previously Treated Multiple Myeloma
Authors: Christoph Heuck, Yogesh Jethava, Rashid Z Khan, Scott Miller, Alan Mitchell, Donald Johann, Kelly Robbins, Ryan K Van Laar, Siraj Ali, Vincent A. Miller, Clyde Bailey, Jeffery Sawyer, Maurizio Zangari, Frits van Rhee, Faith E Davies, Gareth J Morgan, Bart Barlogie
Journal: Blood (2014)