tbuckley/cabot-search huggingface dataset:
Impact of epoetin beta on the survival of anemic patients with ovarian cancer receiving platinum-based chemotherapy
Authors: N. Reed, S. Chan, C. Hayward, H.-U. Burger, W. Ten Bokkel Huinink
Journal: Journal of Clinical Oncology (2005)

5102 Background: Recent meta-analyses in anemic patients with cancer have shown that epoetins do not have a negative impact on survival and show a trend towards reducing the risk of disease progression (Bohlius et al The Cochrane Library 2004; Coiffier et al Ann Oncol 2004; Aapro et al Ann Oncol 2004). The objective of this retrospective study was to provide a follow-up analysis of survival in patients with ovarian cancer who were included in a previous randomized, controlled study of epoetin beta (ten Bokkel Huinink et al Med Oncol 1998). Methods: This was a retrospective analysis of data taken from a randomized, 3-arm study of the use of epoetin beta to prevent anemia in ovarian cancer patients with a hemoglobin [Hb] <13 g/dl. Patients received platinum (Pt)-based chemotherapy (CT) and were randomized to epoetin beta 150 IU/kg or 300 IU/kg three times weekly or no epoetin. The effects of epoetin beta on tumor progression, survival and thromboembolic events were analyzed by standard Kaplan-Meier methods, Cox regression and log-rank tests. Results: A total of 120 patients were included in this analysis (epoetin beta, n=83). Treatment groups were well balanced with regard to demographic characteristics. Epoetin beta was effective at reducing the time to first transfusion and the overall transfusion requirements. The number of occurrences of tumor progression was marginally lower in patients receiving epoetin beta than control (9.6 vs 10.8%) and there was a 17% reduction in risk of progression among patients treated with epoetin beta (hazards ratio [HR] 0.83, 95% CI 0.25, 2.74). A similar proportion of patients in the epoetin beta (6%) and control (5.4%) groups died during follow-up. There was no increased risk of death associated with epoetin beta (HR 1.06, 95% CI 0.20, 5.45). The rate of thromboembolic events (TEEs) was slightly higher in the epoetin beta group than control (7.2 vs 5.4%), but there was no increase in TEE mortality. Conclusions: Epoetin beta may be associated with a reduced risk of tumor progression and has no negative effect on survival in anemic patients with ovarian cancer, who are receiving Pt-based CT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd. Hoffmann-La Roche Ltd.
Using NBN to predict biochemical relapse following image-guided radiotherapy (IGRT) for intermediate-risk prostate cancer (IR-PCa).
Authors: Alejandro Berlin, Emilie Lalonde, Gaetano Zafarana, Jenna Sykes, Varune Rohan Ramnarine, Wan Lam, Alice Meng, Michael Milosevic, Theodorus van der Kwast, Paul C Boutros, Robert Glen Bristow
Journal: Journal of Clinical Oncology (2014)

26 Background: Despite the use of clinical prognostic factors, 20 to 40% of patients with intermediate-risk prostate cancer (IR-PCa) fail local treatment for unexplained reasons. Given that an accurate DNA damage response (DDR) may be associated with genetic instability and radioresponse, we investigated whether copy number alterations (CNAs) in DDR genes are predictive or prognostic following local treatment. Methods: Using array comparative genomic hybridization (aCGH), we characterized CNAs in biopsies derived from 126 IR-PCa pts. who underwent image-guided radiotherapy (IGRT). We studied the DDR-sensing genes: MRE11A, RAD50, NBN, ATM, and ATR. The IGRT cohort (median dose: 76.4Gy; median follow-up: 7.8yrs) was compared to a radical prostatectomy (RP) cohort (154 pts. from Memorial Sloan-Kettering Cancer Center database; median follow-up: 4.8yrs). CNAs were then tested for their independent prognostic capability using Kaplan-Meir method and Cox proportional hazard models. Results: In our IGRT cohort, m,ost frequent DDR gene CNAs were: NBN 20 of 126 (15.9%), ATR 11of 126 (8.7%), and ATM 7 of 126 (5.5%). NBN CNAs were mainly gains (19/20) and strongly correlated with increased NBN-mRNA abundance compared to NBN-neutral cases (p=0.016). CNAs in DDR genes were not associated with GS, prostate-specific antigen, or T-stage. Importantly, NBN gain ranked among the top 3.3% of all genes in terms of its strength of association with the percent of the genome altered (PGA). After adjusting for clinical factors in a multivariate model, NBN gain was a significant independent predictor of 5 years-biochemical relapse-free rate (bRFR) following IGRT (48.6% versus 78.8%; HR = 3.14, 95% CI: 1.42-6.94, p=0.004). No DDR CNA was prognostic in the RP cohort. Increased NBN mRNA expression correlated to radioresistance in vitro (i.e. clonogenic surviving fraction after 3Gy) in five prostate cancer cell lines (R 2 = 0.665). This relationship was not observed for any of the other DDR genes. Conclusions: NBN copy number gain or increased expression correlates with tumor genomic instability, decreased bRFR (IGRT- but not surgery-treated pts.) and intrinsic prostate cancer cell radioresistance. If validated in independent IGRT cohorts, NBN gain could be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches.
Frequency and Clinical Presentation of Polycomb Repressive Complex 2 (PRC2) Component Mutations in Childhood Acute Lymphoblastic Leukemia
Authors: Thomas Ernst, Vivien Schäfer, Jenny Rinke, Anja Waldau, Susan Wittig, Jana Ernst, Ralf Häfer, James F Beck, Andreas Hochhaus, Bernd Gruhn
Journal: Blood (2012)
HER pathway gene expression analysis in a phase II study of pertuzumab + gemcitabine vs. gemcitabine + placebo in patients with platinum-resistant epithelial ovarian cancer
Authors: L. Amler, S. Makhija, T. Januario, U. A. Matulonis, A. Strauss, D. S. Dizon, M. X. Sliwkowski, M. Dolezal, B. Tong, V. Paton
Journal: Journal of Clinical Oncology (2008)

5552 Background: Pertuzumab (P) is a humanized monoclonal antibody that inhibits HER2 heterodimerization. A randomized phase II trial (N=130) of pertuzumab + gemcitabine vs. gemcitabine + placebo in patients with platinum-resistant (CDDP-R) epithelial ovarian cancer (EOC) suggested that pertuzumab could prolong PFS (HR 0.66, 95% CI 0.43, 1.03) and that the duration of PFS may be associated with HER3 gene expression. Final data for overall survival from this trial are presented. Methods: Patients with CDDP-R EOC were randomized to G+P or G+placebo. Treatment was given until progression or until unacceptable toxicity. The primary endpoint was PFS. A secondary objective was to evaluate efficacy outcomes in patients with HER2 activation-related expression profiles. A qRT-PCR assay using archival formalin-fixed paraffin-embedded tissue (FFPET) allowed mRNA expression analysis of HER pathway genes, including HER1, HER2, HER3, amphiregulin, and betacellulin. Outcomes were described by low gene expression (<median) and by high gene expression (>median). Results: Of the 5 biomarkers tested, only HER3 gene expression suggested a patient subgroup with a differential PFS and OS outcome based upon low vs. high results. Final PFS and OS outcomes for all patients and by qRT-PCR HER3 outcomes are as follows in the table below. Conclusions: This exploratory analysis suggests that low tumor HER3 gene expression levels may be prognostic in patients with CDDP-R EOC. Pertuzumab treatment may add to gemcitabine's clinical activity in patients whose tumors have low HER3 gene expression. These data suggest that HER3 mRNA expression levels may be a potential prognostic and predictive diagnostic biomarker. G + P G + Placebo Hazard Ratio (95% CI) PFS (median months) All Patients (n=130) 2.9 2.6 0.66* (0.43, 1.03) Low HER3 (N=61) 5.3 1.4 0.34 (0.18, 0.63) High HER3 (N=61) 2.8 5.5 1.48 (0.83, 2.63) OS (median months) All Patients (n=130) 13.0 13.1 0.91* (0.58, 1.41) Low HER3 (N=61) 11.8 8,4 0.62 (0.35, 1.11) High HER3 (N=61) 16.1 18.2 1.59 (0.8, 3.2) * All-patient analyses were stratified by ECOG status, disease measurability and # prior regimens for CDDP-R disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc., Roche Diagnostics Genentech, Inc. Genentech, Inc. Genentech, Inc.
Gastrointestinal toxicities following radiation therapy for localized prostate cancer.
Authors: G. L. Lu-Yao, S. Kim, D. Moore, W. Shih, Y. Lin, S. Shen, H. Li, M. Dolan, Y. Shao
Journal: Journal of Clinical Oncology (2011)

64 Background: Radiation therapy (RAD) is commonly employed to treat localized prostate cancer; however, representative data regarding treatment related toxicities compared to conservative management (CM) is sparse. Methods: We performed a population-based cohort study, using Medicare claims data linked to the Surveillance, Epidemiology, and End Results data, to evaluate gastrointestinal (GI) toxicities in men aged 65-85 years treated with either primary RAD or CM for T1-T2 prostate cancer diagnosed in 1992-2005. In this study, only GI toxicities requiring interventional procedures occurring after 6 months of cancer diagnosis were included. Competing risk models were used with the following covariates: year of diagnosis, comorbidity, age, tumor stage, cancer grade, hormone use within 1 year of diagnosis, region, race, poverty and marital status. Results: Among 41,859 patients in this study, 28,021 patients received radiation therapy, 19,287 with external beam radiation therapy (EBRT) alone, and 5,138 with brachytherapy alone. The most common GI toxicity was GI bleeding or ulceration. GI toxicity rates were 6.1% after 3D-conformal therapy (3D-CRT), 2.8% after intensity modulated radiation therapy (IMRT), 2.6% after brachytherapy, 8.2% after proton therapy and 1.1% for CM patients. In the multivariate models, RAD group was associated with a higher hazard of GI toxicities (hazard ratio [HR] 4.68; 95% CI, 3, 93-5.58) than CM. Comparing to 3D-CRT, brachytherapy (HR 0.62; 95% CI, 0.51-0.75) and IMRT (HR 0.67; 95% CI, 0.55-0.82) are associated with a lower hazard of GI toxicities, while proton therapy is associated with a higher hazard of GI toxicities (HR 2.15; 95% CI, 1.45-3.17). Conclusions: Radiation therapy is associated with a higher risk of GI toxicities than CM. Among different modalities of radiation therapy, protons therapy is associated with the highest risk of GI toxicities, followed by 3D-CRT, IMRT, and brachytherapy. The increased GI toxicities for patients with proton therapy may reflect a learning curve in the early years. No significant financial relationships to disclose.
Analysis of the incidence of severe adverse events in Japanese cancer patients receiving outpatient chemotherapy.
Authors: T. Shiozawa
Journal: Journal of Clinical Oncology (2011)

e16567 Background: The outpatient chemotherapy for cancer patients is currently standardized in Japan, however the incidence of severe adverse event (SAE) of outpatient chemotherapy have not been systematically studied in a large population. To document the incidence and characteristics of outpatient chemotherapy-induced SAE, we performed a single-institute prospective study about the incidence of SAE in cancer patients receiving outpatient chemotherapy. Methods: The SAE was defined as outpatient chemotherapy related toxicity which was necessary for hospitalized care. From October 2007 to October 2010, a total of 36,034 outpatients chemotherapy were performed at National Cancer Center Hospital East. The incidence and characteristics of every SAE were analyzed. Results: The most common regimens performed as outpatient chemotherapy were gemcitabine (26%), FOLFOX with or without bevacizumab (23%), paclitaxel (10%), docetaxel (9%), FOLFIRI with bevacizumab (7%), irinotecan (5%), and cyclophosphamide plus doxorubicin (4%) and so on. The SAEs were occurred in 306 cases and the incidence of SAE was 0.85%. The most common SAE were hematologic and gastrointestinal toxicities, and infectious disease such as febrile neutropenia (19%), anorexia (16%), diarrhea (16%), and infections (14%). According to the chemotherapy regimens which were performed more than 100 cases, the incidence of SAE were 3.9% in cisplatin plus gemcitabine, 3.3% in TS-1, 2.0% in CHOP, 1.4% in amrubicin, 1.3% in vinorelbine, and 1.1% in irinotecan. Eleven patients (0.03%) experienced SAEs that resulted in death: six patients died of interstitial pneumonia, two of pneumonia, and one of each failure, liver failure and septic shock. Conclusions: This is the first report confirming a low incidence of SAE in Japanese patients undergoing outpatient chemotherapy. To manage outpatient chemotherapy safely, it is most important to control gastrointestinal and infectious toxicities. The spread of hotline service between patients and hospital which makes it possible to take any information on toxicities immediately is now promoted in Japan.
Expression of Programmed Cell Death 1 and Programmed Cell Death Ligand 1 in Extranodal NK/T-Cell Lymphoma, Nasal Type
Authors: Jae-Cheol Jo, Yunsuk Choi, Hee Jeong Cha, Eun Hee Lee, Eun Kyoung Kang, Hawk Kim
Journal: Blood (2015)
Curative-intent surgery for pancreatic tumors: A review of 3,386 procedures from the Brazilian National Health System.
Authors: Lucas Vieira dos Santos, Joao Paulo Lima, Luciola De Barros Pontes, Cleyton Zanardo de Oliveira, Gilberto Lopes
Journal: Journal of Clinical Oncology (2015)

246 Background: In Brazil, a large country with major socioeconomic and health access disparities, resource limitations make the management of pancreatic tumors challenging. We aimed to evaluate curative-intent surgical procedures for pancreatic cancer (PC) in the public health care system. Methods: Based on Brazilian’s public health system database (DATASUS) and demographic database (IBGE), we collected data for curative-intent surgical procedures for pancreatic tumors. Information about number of procedures, costs, length of stay, number of perioperative deaths and PC deaths were analyzed for each State and Region and then correlated to State specific population, gross domestic product (GDP) per capita and number of procedures. Results: Between 2008 and 2012, 37,142 patients died due to PC in Brazil, with an increase of 6.3% in mortality annually. Mortality (per 100,000 persons-year) increases from North to South States. GPD per capita (rho=0.636, 2-tailed p&lt;0.001) was associated to PC mortality. Between January 2008 and July 2014, 3,386 procedures were performed, the majority (51.2%) in the Southeast region (particularly in São Paulo State, 32.7%). Total cost was US$ 9,741,315.28, average cost per admission was US$ 2,876.94. The number of procedures per 100,000 residents was higher in Southeast and South Brazil. On multivariate analysis, average cost in each State was only correlated to the number of procedures (β=0.568, p=0.029). The mean length of hospital stay was 16.9 days, with no major differences across regions. The mean length of hospital stay was correlated to GDP per capita and number of procedures. However, no independent association was found on multivariate analysis. A total of 493 patients died, translating into an inpatient mortality rate of 14.55%, higher than observed in high-income countries. The Northern States have the highest mortality rates (mean 25%, and 33% for the State with highest mortality). Neither characteristic was associated to perioperative mortality. Conclusions: This is the first study to evaluate regional disparities in PC care and mortality in Brazil. These disparities calls for regionalized policies aiming the improvement of PC care.
Improved survival in chronic myeloid leukemia (CML) since introduction of imatinib therapy: A single-institution experience in 1,570 patients referred within 1 month from diagnosis.
Authors: A. Quintas-Cardama, J. E. Cortes, E. Jabbour, S. M. O'Brien, G. Garcia-Manero, J. Shan, F. Ravandi, S. Faderl, T. M. Kadia, G. Borthakur, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6557 Background: The IRIS trial in newly diagnosed CML did not show a survival advantage for imatinib vs interferon, due to the cross-over design. We have used imatinib as frontline CmL therapy since 2001. The study aim is to evaluate the survival benefit in our single institution experience in CML since the introduction of imatinib. Methods: A total of 3,548 patients with CML referred to our institution (1965 – 2010) were reviewed: 2,465 chronic phase (CP), 640 accelerated phase (AP), 443 blastic phase (BP). For this analysis we considered only patients referred within 1 month from diagnosis: 1,149 early CP (ECP); 171 AP; 250 BP. Patients were divided by year of referral. Results: Overall median survival 6.7 years. Median overall survival (OS) in ECP 8 years, AP 4.5 yrs, BP 6 mo. Outcome by year of therapy is shown below (Table). In ECP, OS was significantly different by age overall (p=0.02), particularly in years <2000 (p=0.01), but less significant since 2001 (p=0.07). OS in ECP was also significantly different by Sokal risk group before 2000 (p=0.001), but not since 2001 (p=0.4). No difference by gender. In AP, survival by age was not different in years <2000 (p=0.28); since 2001 OS is significantly better in patients <70 years vs older (p=0.004). In BP, OS was significantly improved over the years (p<0.001), (although 1-yr survival since 2001 is only 34%. OS in BP was not significantly different by age, overall, and in years <2000; since 2001, patients <50 yrs did significantly better (2-yr survival 33% vs <6% for others; p=0.0001). Conclusions: OS in CML significantly improved since 2001 in all CML phases, dramatically so in ECP and AP. Imatinib effective therapy minimized impact of older age and Sokal risk groups in ECP, and accentuated impact of younger age = better prognosis in AP and BP. ECP AP BP Year N % 8 yr OS N % 8 yr OS N 1 yr % <1975 106 6 21 10 13 8 1975-1982 111 15 25 6 29 7 1983-1990 165 42 24 13 41 17 1991-2000 353 65 56 48 83 28 2001-present 414 84 45 78 84 34
Allogeneic Transplant with Reduced Intensity Conditioning Regimens (RIC) Could Reverse Poor Prognosis of Unmutated Igvh, 11q- or 17p- Abnormalities in B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: M.D. Caballero, J.A. García-Marco, R. Martino, M.V. Mateos, R. Cabrera, J. Briones, M. González, J. Esteve, A. León, Josep Maria Ribera, J. Sarrá, J. de la Serna, J.F. San Miguel
Journal: Blood (2004)
Treatment compliance in older patients with melanoma.
Authors: S. Lewin, P. Pugliani, C. R. Pameijer
Journal: Journal of Clinical Oncology (2010)

e19655 Background: Melanoma is a heterogeneous disease that affects patients across a wide age range. The National Comprehensive Cancer Network (NCCN) guidelines recommend wide excision and sentinel node biopsy (SNB) for any lesion classified T1b or greater, regardless of patient age. Patients with regional disease should undergo complete lymph node dissection (CLND). This study describes the age-related variations in NCCN compliance at our cancer center. Methods: From 2006 to 2009, the cancer center's melanoma registry was used to describe the patient/tumor characteristics, physician recommendations, patient choices and outcomes. Results: All melanoma diagnoses were confirmed by biopsy. Since 01/2006, there were 171 total melanoma cases in patients over age 70, with 147 (86%) biopsy-confirmed lesions. Overall, the compliance rate was 84.4%. This rate was lower for older (50/69, 72.5%) versus younger patients (74/78, 94.9%). The average age of NCCN compliant patients was 78, versus 86 years (noncompliant patients). Treatment of older patients was not compliant with resection margins in two cases (2/171, 1%). Among the 19 SNB noncompliant patients, 50% had an ulcerated lesion and 58% had a nodular melanoma. Only one of the 19 older patients was not offered a SNB. Commonly, reasons for no SNB included patient refusal (14/19, 74%) or no localization on lymphoscintigraphy (4/19, 21%). Of the 50 older patients with SNB, 10 (20%) had a positive sentinel node. Of these, 2 patients (20%) refused CLND. Six month overall survival among non-compliant patients was 79%, versus 96% in the compliant patients (p<0.05). Conclusions: Our institution's NCCN compliance compares favorably with published rates. Largely by their own choice, older patients appear less likely to undergo sentinel node biopsy as compared to younger patients. Further research appears warranted to evaluate the impact of patient choices for NCCN compliance upon risk-adjusted survival rates. No significant financial relationships to disclose.
Reinitiating <i>nab</i>-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer.
Authors: Erkut Borazanci, Katy Schroeder, Gayle S. Jameson, Ramesh K. Ramanathan, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2014)

381 Background: The recent results of the phase III trial MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) demonstrated an improvement in progression free survival, overall response rate, and overall survival for the combination of nab-paclitaxel plus gemcitabine compared to gemcitabine alone. Methods: A retrospective analysis of patients with advanced pancreatic adenocarcinoma was undertaken to determine the disease control rate (CR+PR+SD ≥ 16 weeks) in patients who had received prior nab-paclitaxel plus gemcitabine and were retreated with nab-paclitaxel plus gemcitabine again after receiving other interval therapies. Results: Nine patients were identified. The median time between treatments of nab-paclitaxel plus gemcitabine was 7.67 months (range 2.53 to 54.03 months). The regimens used in between treatments of nab-paclitaxel plus gemcitabine were 5FU-based in 8 of the 9 patients, with the other patient undergoing temozolomide, cetuximab, and sorafenib sequential treatment. Five of the nine patients received repeat nab-paclitaxel plus gemcitabine &gt; 6 months after their initial nab-paclitaxel/gemcitabine regimen and four of the nine received repeat nab-paclitaxel plus gemcitabine &lt; 6 months after their initial nab-paclitaxel/gemcitabine regimen. The disease control rate seen for the second treatment with nab-paclitaxel plus gemcitabine was 44% (four of nine patients). Two of these patients received repeat nab-paclitaxel plus gemcitabine &lt; 6 months after their first nab-paclitaxel plus gemcitabine regimen and two of these patients received repeat nab-paclitaxel plus gemcitabine &gt; 6 months after their first nab-paclitaxel plus gemcitabine regimen. Three of nine patients (33%) had treatment a third time with nab-paclitaxel plus gemcitabine, with 2 of 3 of these patients having disease control. As of September 1st, 2013, two of nine patients are still undergoing repeat nab-paclitaxel plus gemcitabine therapy. Conclusions: Nab-paclitaxel plus gemcitabine can be an effective repeat regimen in patients with advanced pancreatic adenocarcinoma. In this very small series, the time between reinitiation of nab-paclitaxel plus gemcitabine appears to not play a role in disease control rate.