tbuckley/cabot-search huggingface dataset:
Malignant ovarian germ cell tumors: A retrospective analysis of the Russian Cancer Research Center
Authors: O. Streltsova, M. Fedjanin, A. Bulanov, K. Zhordania, V. Kuznetsov, S. Tjulandin
Journal: Journal of Clinical Oncology (2008)

16105 The aim of this study was to analyse treatment results of patients with malignant ovarian germ cell tumors (MOGCT) between 1990 and 2006. A total of 117 patients with MOGCT were retrospectively reviewed. The histologic subtypes included dysgerminomas (n=35), endodermal sinus tumors (n=26), immature teratomas (n=19), embryonal carcinoma (n=3), polyemryoma (n=1), benign struma ovarii (n=1), mixed germ cell tumors (n=29). Tree patients had no morphologic verification. Primary locations were as follows: ovary 114 pts and extragonadal 3 pts (retroperitoneum in 2 cases, mediastinum in 1). 60 pts had primary treatment in NNBRCRC during the period 1990–2006 and referred for follow- up (n=7) or salvage therapy after recurrence (n=50). The median (range) age at presentation was 21 (14–42) years. 41 women (35%) presented with FIGO surgical stage I disease, 8 (5,1%) had pelvic metastases (stage II), and 38 (32,5%) had advanced (stage III/IV) disease. 30 pts had no comprehensive surgical staging. 8 women had evidence of dysgenetic gonads with a 46 XY karyotype. Primary surgery was done in 114 pts. 3 pts received neoadjuvant chemotherapy with followed surgery in two pts. 58 (51%) pts underwent fertility-sparing surgery. Among the 60 women who received 1st line chemotherapy ± surgery in NNBRCRC 51 (85%) are alive without evidence of disease. The overall survival is 84%, for dysgerminomas - 97% and 78% - for nondysgerminomas at a median follow-up of 58 months. 6 deaths were associated with progressive disease, 2 patients died of severe chemotherapy complications and 1 - of intercurrent disease. It is important to note that only 2 (6%) pts (both with non-dysgerminomas) out of 36 treated in our center since 2000 year died of progressive disease. Among the 53 women referred for salvage therapy to NNBRCRC 43 (81%) women are alive without evidence of disease. 7 (6%) pts received no adjuvant treatment after surgery due to stage Ia dysgerminoma. 5 pts had disease progression, all of them were rescued with platinum-based chemotherapy. 2 are alive without evidence of disease at a median (range) follow-up of 26 months. Our date confirmed that prognosis of MOGCT is excellent if managed with standard treatment initially, that’s possible, as a rule, only in specialized cancer centers. No significant financial relationships to disclose.
Gene expression signatures in non-small cell lung cancer (NSCLC) according to cigarette smoking history
Authors: J. Jassem, A. Szymanowska, M. Skrzypski, R. Rosell Costa, M. Taron, I. Chaib, W. Rzyman, M. Jarzab, T. Muley, E. Jassem
Journal: Journal of Clinical Oncology (2008)

22082 Background: Epidemiological and experimental studies confirm that cigarette smoking is the principal causal agent of lung cancer. It is estimated that about 2–5% of all lung cancer patients (pts) have never smoked. A knowledge on molecular features of lung cancers not related to smoking might lead to better understanding of their carcinogenesis and allow development of new therapeutic targets. In this study we compared gene expression signatures in non-smoking vs smoking NSCLC pts. Methods: Study group included 70 NSCLC pts, of those 25 never-smokers (WHO criteria) and 45 current or past smokers (mean 49.7 pack-years, range 6–130). All pts underwent curative pulmonary resection. There were more women among non-smokers (p=0.003), whereas other major characteristics did not significantly differ between both groups. Qualitative RT-PCR analysis was performed on mRNA derived from snap frozen tumor specimens. Expression of 27 genes: potentially related to smoking, including kinase receptors, sex hormone receptors, transcription factors and genes involved in HPV infection pathways was investigated. 18S rRNA subunit, POLR2A, ESD and YAP1 were used as normalization genes. Gene expressions were compared by parametric permutation test with Benjamini-Hochberg correction for multiple comparisons (False Discovery Rate assessment). Results: In univariate analysis 3 genes were particularly overexpressed in tumors of non-smokers: RRAD (p=0.0002), TGF-beta receptor-2 (TGFBR2; p=0.002) and progesterone receptor (PgR; p=0.007). TGF-beta receptor-3 (TGFBR3; p=0.02), SOX9 (p=0.02) and androgen receptor (AR; p=0.03) were also significantly overexpressed in these tumors. After correction for the impact of sex, histopathology, stage of disease, and multiple comparisons, RRAD and TGFBR2 were independently correlated with smoking history. Conclusions: NSCLC in non-smokers is characterized by a specific gene expression signature. Overexpression of TGFBR2 provides the basis for developing new targeted therapies. No significant financial relationships to disclose.
Whole-body MRI evaluation of tumor burden in the neurofibromatosis tumor suppressor syndromes
Authors: S. R. Plotkin, M. Singh, W. Cai, C. O'Donnell, S. Esparza, M. J. Smith, G. J. Harris, A. Muzikansky, M. A. Bredella, A. Kassarjian
Journal: Journal of Clinical Oncology (2009)

2074 Background: Neurofibromatosis 1 (NF1), NF2, and schwannomatosis are a group of related genetic disorders in which affected individuals share the predisposition to develop multiple neurofibromas and schwannomas. The prevalence of internal tumors is not known because current estimates are based on regional MRI scans that may not detect occult tumors. A rapid and sensitive method to detect internal tumors is highly desirable since they can cause neurologic dysfunction, compress vital structures, or transform into malignant tumors. Whole-body MRI (WBMRI) is an imaging technique by which the entire body can be imaged in a relatively short time without the use of ionizing radiation. Methods: We performed WBMRI in subjects with NF1, NF2, or schwannomatosis as part of an IRB-approved research study. Each subject was imaged from head to ankles in the supine position using a 1.5 Tesla magnet, integrated body coil, and no intravenous contrast. Using five acquisitions, the entire body was imaged using a fat suppressed fluid sensitive STIR sequence. The images were then fused into a single whole body DICOM image. The number and type of tumors (discrete vs. plexiform) were identified by a board-certified radiologist and tumor volume was calculated using semi-automated analysis. Results: A total of 100 subjects were imaged (NF1–50; NF2–25, schwannomatosis-25). Sixty-one percent of subjects had ≥1 internal tumor. The median number of tumors in affected individuals was 5 (range, 1 to 63 tumors). Overall, the legs harbored the greatest number of tumors (33%), followed by the pelvis (18%), thorax (15%), abdomen (12%), arms (10%), and head/neck (7%). Only 40% of internal tumors were classified as plexiform yet these tumors contributed 78% of the tumor burden by volume. Conclusions: WBMRI scan is a powerful tool to evaluate the number, size, and distribution of internal tumors in patients with neurofibromatosis. This technique provides unique phenotypic information for genetic studies on NF1, NF2, and schwannomatosis. In addition, WBMRI may prove useful in identifying individual patients at high risk for complications (such as neurologic dysfunction or malignant transformation) due to heavy internal tumor burden and in determining the efficacy of antitumor drugs in this unique patient population. No significant financial relationships to disclose.
Immune response to gastrin-17 and survival in gastrointestinal cancers.
Authors: J. M. Oortgiesen, L. A. DiMichele, J. R. Weidman, V. T. Gunto, T. Soeder, A. Cato, L. Sutton
Journal: Journal of Clinical Oncology (2010)

e14541 Background: Gastrin is a potential growth factor for tumors arising within the gastrointestinal tract. Polyclonal antibody stimulator (PAS), is a novel immune stimulator that elicits antibodies that neutralize and block the proliferative activity of gastrin-17 (G17) and its precursor, glycine extended G17 (gly-G17). Research with PAS suggest a clinical benefit in patients with an immune response. Data from over 1,200 patients with pancreatic, gastric, and colorectal (CRC) cancers were analyzed to define the relationship between immune response and efficacy and to determine the dependence of this effect on several baseline characteristics related to patients' health status. Methods: PAS was given as a monotherapy or in combination therapy as 3 initial doses, with a booster in some studies. PAS responders were defined by ELISA. The relationships between demographics and baseline disease characteristics and immune response and between immune response and survival were analyzed. Results: In these studies, PAS responders varied between 52% and 89%. In stage II-IV pancreatic responder patients, median survival (MS) was 176d and 63d for nonresponders (p < 0.002, log rank). Stage IV pancreatic responder patients had higher MS compared to nonresponders (167d vs 104d). Similarly, stage I-III pancreatic responders had higher MS (179 d vs. 146 d in nonresponders). For advanced gastric responder patients who received PAS with cisplatin and 5-FU, MS was 303 d compared to 70d for nonresponders (p < 0.001, log-rank). In stage IV CRC with PAS alone, PAS responder patients showed better survival (267 d) than nonresponders (192 d). In metastatic CRC responder patients who received PAS with irinotecan, MS was 249d versus 119d for non-responders (p < 0.001, log rank). Additional analysis showed that responder survival correlation was independent of any covariates. Conclusions: PAS responders had a significantly longer survival rate. This effect was independent of various covariates that predicted the health status of the patients at baseline. The survival benefit for responders and the favorable safety profile indicate that PAS has exciting prospects for an improved anti-cancer treatment for various GI cancers. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cancer Advances, Cato Research
Randomized phase II trial of TACE plus everolimus as first-line therapy in localized unresectable hepatocellular carcinoma (HCC): The TRACER trial.
Authors: Ronnie Tung Ping Poon, Li-Tzong Chen, Hong-Ling Xue, Bayane Tannir, Jia Hua Wang, Tawesak Tanwandee, Seung-Woon Paik
Journal: Journal of Clinical Oncology (2012)

TPS4149 Background: Transcatheter Arterial Chemoembolization (TACE) has shown benefit in improving survival and is a widely used treatment for unresectable HCC. However, TACE induces hypoxia leading to up-regulation of HIF-1α and VEGF signaling, and tumor progression. Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR) and its downstream signaling including HIF-1α. Everolimus has also been shown to increase chemosensitivity of HCC in preclinical study (Cancer Lett; 273(2):201-9). Combining everolimus with TACE may delay tumor progression. TRACER (Tace with Rad001 in Asian Centers for Evaluation and Research) aims to evaluate the efficacy and safety of everolimus plus TACE in patients with localised unresectable HCC. Methods: TRACER is a multinational, randomized, double-blind, placebo-controlled phase II trial. Patients aged ≥18 years newly diagnosed with localized unresectable Child A HCC; ECOG PS of &lt;2; ≥1 unidimensional lesion measurable according to RECIST; and adequate bone marrow, liver, and renal function. Exclusion criteria include main portal vein invasion and/or extrahepatic spread; prior local or systemic treatment for HCC, or contraindications to TACE. Eligible patients who have successfully undergone the first TACE are randomized 1:1 to oral everolimus 7.5mg or matching placebo daily. TACE is repeated every 10 weeks or so. A short everolimus dose interruption of 48 hours before and after each TACE has been designed to allow recovery from complications of TACE. For standardization, doxorubicin-eluting beads are being used in every TACE. Patients shall exit the trial upon tumor progression, unacceptable toxicity, death, or trial discontinuation. All endpoints will be assessed on an ITT basis. The primary endpoint is time to progression base on Modified RECIST Criteria. Secondary endpoints include objective response rate, overall survival, and incidence of extrahepatic spread, safety and exploratory biomarkers. An independent data monitoring committee has been established to safeguard the trial subjects. Estimated total enrollment is 80, of which 12 subjects have been enrolled. (Clinical Trial Registry Number: NCT01379521.)
Nine-weeks of adjuvant trastuzumab in HER2-positive breast cancer: A single center experience.
Authors: Cemal Kizilarslanoglu, Ibrahim Petekkaya, Taner Babacan, Kadri Altundag
Journal: Journal of Clinical Oncology (2012)

e11080 Background: Trastuzumab is an effective adjuvant targeted therapy in patients with HER-2 positive breast cancer. However, effect of this therapy on survival is not well described in literature. In this study, we aimed to show characteristics of patients treated with nine week trastuzumab therapy for breast cancer and survival analysis. Methods: We analyzed the data of 2.218 breast cancer patients treated and followed up in our medical oncology department. There were 165 patients treated with 9 weeks of adjuvant trastuzumab therapy in this cohort. Patients’ characteristics, prognostic factors, and survival data were analyzed by using SPSS 18.0 version. Results: The mean age of the patients at the time of diagnosis of breast cancer was 47.3 ± 10.0 years. Sixty two (37.6%) patients were postmenopausal, eighty two patients (49.7%) were premenopausal and twenty patients (12.1%) were peri-menopausal. Invasive ductal carcinoma was the most common pathological type and was observed in 87.9% of the patients. ER and PR was positive in 49.1% of the patients and 54.5 % of the patients, respectively. Percentage of stage of the patients was 10.9 in stage I, 21.1 in stage IIA, 17.6 in stage IIB, 21.2 in stage IIIA, 0.6 in stage IIIB, 23.6 in stage IIIC. Mean follow up time of the patients was 30.9 ± 13.4 months. Numbers of the patients with progression were eighteen (10.9%). Eight (4.8%) patients died due to disease progression. Two-year survival rate was 98.3%. Disease free, progression free and overall survival times could not be obtained due to inadequate number of events. Conclusions: The superiority of nine weeks of adjuvant trastuzumab therapy to standard one year regimen of adjuvant trastuzumab is not well described in literature. The studies comparing 9-weeks and one year of adjuvant trastuzumab use with large numbers of patients are needed to show which regimen is superior.
Biological Pathways and In Vivo Anti-Tumor Activity Induced by Atiprimod in Multiple Myeloma (MM).
Authors: Paola Neri, Pierfrancesco Tassone, Masood Shammas, Hiroshi Yasui, Ernestina Schipani, Ramesh B. Batchu, Simona Blotta, Rao Prabhala, Laurence Catley, Makoto Hamasaki, Teru Hideshima, Dharminder Chauhan, Gary S. Jacob, Donald Picker, Salvatore Venuta, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2006)
Adjuvant therapy report card: Patients with stage II/III colon cancer grade their oncologists
Authors: N. Love, K. Ault Ziel, C. Bylund, M. Elder, L. M. Ellis, A. Grothey, N. J. Meropol, D. Paley, P. M. Ravdin, L. B. Saltz
Journal: Journal of Clinical Oncology (2009)

4045 Background: Our group previously reported on patient (Pt) recollections of adjuvant therapy (AT) for colon cancer and their grading of medical oncologists (MO) regarding various aspects of care. Overall, MO were highly rated, but grades for presenting information were lower, and patient expectations about side effects often did not match experiences. To further examine the Pt experience with AT, a prospective study was launched in Feb 2008. Methods: Pts with Stage II/III colon cancer about to begin or within 4 months of starting AT were recruited for a 4-part survey regarding sources and quality of treatment information and their experiences with AT. The survey also asked Pts to provide a grade (A-F) for their MO in 8 areas. Results: 85 Pts (71% female, 79% Stage III, median age 52 years) completed Part 1 of the survey. 93% stated that their MO explained the risks and benefits of AT. Of those, 92% stated they understood this information completely or almost completely (3 or 4 on a 0–4 scale) and 79% received numerical estimates of recurrence risk with and without treatment. When questioned about the potential absolute benefit of AT, 26% of Pts who received numerical estimates “had no idea” and other answers ranged from 3% to 100% for recurrence risk. Pt grade point averages for their MO ranged from 3.0 to 3.6 ( Table 1 ). As in the prior survey, expectations about side effects frequently did not accurately reflect experiences. For example, 54% of Pts expected alopecia but only 5% experienced it to a significant degree. 84% of Pts also sought information from websites, and 87% rated this as helpful and valuable (3 or 4 on a 0–4 scale). Conclusions: Pts are generally satisfied with their MO but less so with the presentation of treatment-related information and thus frequently consult additional resources, such as cancer information websites. This suggests an opportunity for improved information delivery within oncology offices and via the Internet. [Table: see text] [Table: see text]
Dietary salt modulates the hypertensive effect of high aldosterone in subjects with resistant hypertension
Authors: Eduardo Pimenta, Krishna Gaddam, Monique N. Pratt-Ubunama, Mari K. Nishizaka, David A. Calhoun
Journal: Circulation (2006)

Introduction: Aldosterone excess raises blood pressure levels and contributes to injury in target organs including the heart, kidneys, and brain. Experimental data suggest that the deleterious effects of aldosterone are dependent upon concomitant high dietary salt ingestion. However, no human studies have evaluated the interaction between dietary salt and hyperaldosteronism. Hypothesis: We tested the hypothesis that ambulatory blood pressure levels are related to the interaction of dietary salt and aldosterone in subjects with resistant hypertension. Methods: One hundred thirty-six subjects with resistant hypertension were prospectively evaluated by measurement of 24-hour urinary aldosterone (Ualdo) and sodium (UNa), and 24-hr ambulatory blood pressure monitoring (ABPM). Daytime, nighttime and 24-hr blood pressure (BP) as well as nocturnal blood pressure decline were determined. Subjects were designated as having high (Ualdo≥12 µg/24h) or normal (Ualdo<12 µg/24h) aldosterone excretion. Subjects were further divided into 3 groups according to urinary salt excretion: low (Una<125 mEq/24h), medium (125≤Una<225 mEq/24h), and high (Una≥225 mEq/24h). Results: Overall, the mean office blood pressure was 160.2/89.8 mmHg on an average of 4.1 medications. There was no difference in mean office BP values between the 72 subjects with normal Ualdo and the 64 subjects with high Ualdo. There was no difference in office and 24-hr BP levels in the normal Ualdo group regardless of urinary sodium excretion. In contrast, in the high Ualdo group, the office diastolic (89.2±2.7 vs 78.5±2.9mmHg, p=0.03), systolic daytime (149.0±3.2 vs 136.8±4.1mmHg, p=0.03), diastolic daytime (86.9±2.2 vs 77.3±2.9 mmHg, p=0.01), systolic nighttime (143.1±3.2 vs 127.7±5.4 mmHg, p=0.01), diastolic nighttime (81.4±2.3 vs 69.4±3.6 mmHg, p=0.006), 24-hour systolic (146.8±3.0 vs 133.4±4.1mmHg, p=0.01), and 24-hour diastolic (84.6±2.1 vs 74.5±3.2mmHg, p=0.01) BP were all higher in high compared to low urinary sodium excretion group. Conclusion: Reduced dietary salt ingestion blunts the hypertensive effects of high aldosterone levels. This is the first demonstration that dietary salt ingestion significantly modulates the clinical effects of aldosterone in humans.
A phase II study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (ER-CHOP) in patients with previously untreated diffuse large B-cell lymphoma
Authors: I. N. Micallef, M. J. Maurer, D. A. Nikcevich, M. Cannon, D. F. Moore, P. Kurtin, T. E. Witzig
Journal: Journal of Clinical Oncology (2008)

8500 Background: A prior pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy (ER-CHOP) in untreated patients with diffuse large B-cell lymphoma demonstrated feasibility and safety. This multicenter phase II study was carried out to assess efficacy. Methods: Patients received chemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. Weekly blood counts were obtained to monitor hematological toxicity. Primary endpoint was 12 month event free survival (EFS12). Secondary endpoints were complete response rate (CR), overall response rate (ORR). An interim analysis was planned when the first 34 eligible patients are evaluable for EFS12. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 29 patients were ineligible based on CD22 negative (11), inadequate pathology or transformed histology (17), or cancel (1) resulting in 78 evaluable patients. Baseline patient characteristics for the entire patient population included median age 62 (range 21–82); 59 patients were male. Most patients had advanced stage (82%); majority had low or intermediate IPI. 72 (67%) patients had an elevated LDH. Performance sore was 0–1 in 94 pts and 2–3 in 13 pts. Overall, 104 patients are evaluable for toxicity. 71 patients (68%) developed grade 4 neutropenia, grade 3 or 4 anemia (9%) and thrombocytopenia (13%). Non- hematological adverse events included neuro-sensory (45%), fatigue (36%), and vomiting (28%). The most common grade 3 or 4 treatment related event was febrile neutropenia (17%). This study has met full accrual. At the time of the planned interim analysis, response rate for these 34 patients is 16 CR, 3 CRu (56% CR + CRu), 13 PR (38%), and 2 SD with an ORR of 94%. Data on the primary endpoint (EFS12) is still maturing and will be reported at the meeting. Conclusions: ER-CHOP every 21 days is safe. The ORR is encouraging; further analysis will determine if this regimen should be evaluated in a phase III randomized study. No significant financial relationships to disclose.