tbuckley/cabot-search huggingface dataset:
Abstract 12411: Prognostic Value of Cardiovascular Magnetic Resonance-Derived Indices of Right Ventriculo-Arterial Coupling and Internal Mechanical Work in Pulmonary Hypertension
Authors: Amr Abouelnour, Mark Doyle, Diane Thompson, June Yamrozik, Ronald Williams, Moneal Shah, Siva K Soma, Srinivas Murali, Raymond Benza, Robert W Biederman
Journal: Circulation (2014)

Objectives: External cardiac work performed is represented by the area within the ejection loop (P-V) and correlates poorly with the heart’s total energy demands until the internal work component is added. Further, the ratio of the arterial elastance (E a ) to the ventricular end-systolic elastance (E max ) is a measure of ventriculo-arterial coupling. We investigated the impact of both indices of right ventricular (RV) performance on outcome in patients with pulmonary hypertension (PH). Methods: Cardiac magnetic resonance (CMR) studies of a retrospective consecutive cohort of 115 PH pts (61±14 yrs) were examined for RV volumetrics, functional indices and the presence of RV late gadolinium enhancement (LGE) from 2008-2014. Right heart cath (RHC) parameters were included in the analysis (performed within 1±1.5 mo of CMR) as was 3D RV mass and RVEF. The E a /E max ratio was derived in part as RV end-systolic volume (ESV)/RV stroke volume. Internal mechanical work was estimated as RVESV*(RV-ES pressure- RV-ED pressure). Patients were followed up to 5 yrs. Results: During follow-up, 42/115 (37%) pts had a MACE. On a multivariable logistic regression analysis, the strongest predictor of MACE was the internal RV mechanical work followed in order by E a /E max versus mean pulmonary artery pressure, RV mass, RV EF, and RV LGE. The strongest predictors of time to MACE were the RV internal mechanical work (χ 2 =10.8) and E a /E max ratio (χ 2 =9.2). Kaplan-Meier analysis of time to MACE for quartiles of RV internal mechanical work and E a /E max are shown in Figure 1A &amp; B. Conclusions: Higher RV internal mechanical work and E a /E max are both markers for worsening prognosis in PH patients; E a /E max having the added advantage of being an entirely non-invasive CMR derivation and statistically equivalent. Both metrics were superior to standard clinical metrics including RV LGE, RVEF, PA pressure and RV mass and for the first time address integrated cardio-pulmonary physiology as early markers for MACE.
Radiation and survival in women over 70 with T1 N0 M0 ER-negative breast cancer from 1990 to 2007: A population-based analysis.
Authors: A. P. Wojcieszynski, X. Shen, M. V. Mishra, P. R. Anne, T. N. Showalter
Journal: Journal of Clinical Oncology (2011)

1037 Background: The role of radiation therapy (RT) is controversial in older women (age ≥ 70) undergoing breast conserving therapy. While there is data that the omission of RT in women over 70 with estrogen receptor (ER) positive tumors who receive endocrine therapy is not associated with a survival difference, limited data exists for ER negative tumors in older women who undergo breast conservation. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify women age ≥70 years diagnosed with Stage I invasive ductal breast cancer from 1990 – 2007 treated with lumpectomy. We extracted data on patient demographics, tumor characteristics, initial treatment, and survival. Breast cancer mortality (BCM) was defined as length of time from diagnosis to death by breast cancer, censored at last follow-up or death from other cause. We used the log-rank test to compare BCM, logistic regression to determine predictors of radiation use, and Cox proportional hazards model to determine the predictors of BCM. Results: We identified 26,652 older women (age ≥70) with Stage I invasive ductal breast cancer treated with lumpectomy. There were 2,882 (10.8 %) women with ER negative tumors. In this group, most patients (68.4%) received external beam RT, while 23.7 % received no RT. Among ER negative women, significant predictors of omission of RT were older age (Odds Ratio (OR) 1.37 CI 1.26−1.49 per 5 years), and failure to perform a pathologic lymph node evaluation (OR 2.82 CI 2.25−3.52). BCM rate at 5 years was reduced in patients with ER negative tumors treated with RT compared to no RT (5.6% vs 15.1%, p<0.001). On multivariate analysis, we found that omission of RT was associated with a 91% increased likelihood of BCM (Hazard Rate (HR) 1.91, p <0.001); other significant predictors of BCM were poorly differentiated grade (HR 1.46 p = 0.01), size > 1 cm (HR 1.70 p<0.001), and failure to perform a lymph node examination (HR 1.79 p<0.001). Race and income were not significant predictors of BCM among women with ER negative tumors. Conclusions: Adjuvant RT after lumpectomy significantly reduces BCM in women older than 70 with Stage I, ER negative breast cancers. RT is currently underutilized in these women.
Phase I study of everolimus in combination with fluvastatin and zoledronic acid in patients with solid tumours.
Authors: Charlotte Rose Lemech, Antoinette Fontela, Hendrik-Tobias Arkenau, Melvin T.M. Chin, Sandra Li, Winston S. Liauw, David Thomas, Paul L. De Souza
Journal: Journal of Clinical Oncology (2012)

e13585 Background: Everolimus (E) is an mTOR inhibitor with broad anti-tumour clinical activity. There is preclinical evidence of synergistic activity through the combination of E with fluvastatin (F) and zoledronic acid (ZA). F, an HMG CoA reductase inhibitor, and ZA, a bisphosphonate, have both been shown preclinically to inhibit isoprenylation (addition of hydrophobic molecules) of key signalling proteins with subsequent inhibition of the Ras pathway. We investigate their potential activity further in this open-label phase I trial. Methods: Patients (pts) with advanced solid tumours were treated with escalating doses of E, F and ZA to evaluate safety, clinical activity, pharmacokinetics (PK), pharmacodynamics (PD) and the recommended dose for further study. PK samples were obtained over 24 hrs on day 1 and 8 of cycle 1 and day 1 of cycle 2. Pre- and post-dose PBMCs were analysed for markers of MAPK and PI3K-AKT-mTOR pathways (pERK, pAKT and pS6). Results: Maximum doses of each drug in combination (DL 4) were feasible and no DLTs were observed. Of the 16 pts evaluable [median age=63yrs (range 47-81)], the median number of cycles was 3.8 (range 1-8), with 44% of pts receiving ≥ 4 cycles. Drug related toxicities were mainly G1/2, many within the expected toxicity profile of E, including fatigue (12 pts, 75%), myalgias (9 pts, 56%), anorexia (8 pts, 50%), infection (8pts, 50%), dyspnoea (7pts, 44%), diarrhoea (7 pts, 44%), nausea (7 pts, 44%), peripheral oedema (5 pts, 31%) and mucositis (4 pts, 25%). G3 adverse events were predominantly due to symptoms of disease progression. G1/2 anemia and thrombocytopaenia were the most common haematological toxicities, particularly in DL 3 and 4. 44% of pts achieved stable disease as best response (mean 4.5m [range 3-6m]); including 2 CRC pts (DL 4) and 2 CRPC pts (DL 3 and 4). PK and PD results will be presented in further detail. Conclusions: The combination of E/F/ZA is feasible without any added or overlapping toxicities in this phase 1 study. [Table: see text]
Breast cancer patients (BCP) with liver metastases (LM). Clinical experience at one institution
Authors: J. W. Zinser, C. Cano, F. Lara, J. Velasco, H. López-Basave, A. Alvaradp, N. Castañeda, F. Morales
Journal: Journal of Clinical Oncology (2004)

856 Background: Despite the progress in the treatment of breast cancer, patients with visceral metastatic disease have a poor prognosis. Nevertheless, BC with LM have a median survival of 14 months without prior therapy and a better outcome when they have no other site of metastases (Zinser et al. JCO 1987;5:773–82). We describe a 5-year experience at our institution. Patients and Treatment: Between 01/95–12/99 187 BCLM were identified with histologically confirmed diagnosis of breast cancer and measurable hepatic disease by imaging studies. Results: Mean age 48 year (26–86). PS-1 (WHO): 70%, initial stage: I-IIIB 56% IV 44%. Postmenopausal 59%. Liver as only site of metastases in 7%, two sites 44% and ≥3 49%. Therapy prior to LM: 126 (67%) anthracycline based chemotherapy, XRT 76 (40%) and tamoxifen 103 (55%). Five patients with LM received no further therapy. Treatment for LM was: anthracycline based chemotherapy in 173 (95%), taxanes 3%, other 2%. One case was treated with surgical resection plus chemotherapy. Median survival was 13.6 months. Multivariate analysis revealed poorer survival for initial advanced clinical stage RR1.7 (IC95% 1.18–2.50) and number of organ sites involved by metastases 2.6 (IC95%1.5–4.6). Conclusions: The overall median survival of our patients in spite prior anthracycline therapy was similar to reported patients without prior therapy. However tumor volume represents a poorer prognostic factor. With the introduction of new drugs it is conceivable that prognosis may improve even further. No significant financial relationships to disclose.
Pharmacokinetic (PK) interaction of ketoconazole (KC), clarithromycin (CM) and midazolam (MZ) with riociguat
Authors: Corina Becker, Reiner Frey, Sigrun Unger, Dirk Thomas, Michael Reber, Gerrit Weimann, Hartmut Dietrich, Erich R. Arens, Wolfgang Mueck
Journal: European Respiratory Journal (2013)

Introduction   Riociguat, an oral sGC stimulator, is under investigation for PH treatment. CYP-mediated oxidative metabolism is one of the major riociguat clearance pathways.   Aims   Riociguat PK studies with KC (multi-pathway CYP and P-gp/BRCP inhibitor), CM (CYP3A4 inhibitor), and MZ (CYP3A4 substrate) investigated any interactions.   Methods   Open-label, randomized, crossover studies in healthy males were: 1) 4–day KC 400 mg od then 1–day KC 400 mg od ± riociguat 0.5 mg (n=16); 2) 4–day CM 500 mg bid then 1–dose CM 500 mg ± riociguat 1 mg (n=14); 3) 3–day riociguat 2.5 mg tid then 1–day riociguat 2.5 mg tid ± MZ 7.5 mg (n=24).   Results   Riociguat PK data from the KC and CM studies are shown below.  Riociguat pre- and co-treatment did not alter MZ AUC or C max  (90% CIs for ratio riociguat + MZ / MZ within pre-specified 80–125% range).  The most common AEs with riociguat +/- KC, CM, and MZ across the 3 studies were headache (17%) and dyspepsia (10%). 1 SAE occurred in the MZ study (elevated creatine phosphokinase; not drug-related).   Conclusions   Use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors (eg KC) is not recommended. CM moderately increased riociguat AUC without significant change in C max  (not considered clinically relevant). No PK interaction was seen between riociguat and MZ.
Communication of BRCA1/2 test results to first-degree relatives (FDRs): Factors predicting who women tell
Authors: M. Dorval, L. Digianni, J. E. Garber, A. F. Patenaude
Journal: Journal of Clinical Oncology (2004)

1010 Background: Patient communication with relatives about cancer genetic test results is the primary means for alerting those who may benefit from identification of hereditary risk status. Awareness of factors predicting sharing of genetic information may help providers encourage optimal dissemination. This study identifies factors predicting which FDRs women tested for BRCA1/2 mutations inform about their result. Methods: 273 women participating in a randomized trial of counseling methods completed a specially-designed family communication measure 4 months after BRCA1/2 results disclosure (n=68 positive, 34 negative, 171 indeterminate or variant). Logistic regression models were used to identify factors predicting sharing of test result. Potential predictors included test result, participant age and cancer status, lineage affected by BRCA1/2, counseling method, mother and father cancer status, and offspring gender and age. Results: Most FDR's were told the participant's test result by 4 months. Regardless of test result, female relatives appeared more likely to be informed than males. In the sub-group of mutation-positive women, where telling may be most critical, 96% told mothers, 82% fathers, 90% told all sisters, 75% all brothers, 100% daughters =18, 92% sons =18. Logistic regressions of data on all women suggest those = age 40 were more likely to share their result with their mother (p < 0.02), father (p < 0.05) and sisters (p=0.04) than were older women. Telling brothers was more likely when BRCA1/2 was inherited through paternal lineage (p=0.07). Participant age (p<0.001), children's ages (p<0.001)and gender (p=0.02) influenced communication of test result to offspring. Conclusions: Demographic and health-related factors, but not BRCA1/2 result, predicted genetic test result communication to FDRs. By 4 months post disclosure, nearly all female relatives had been informed. Providers may need to stress the potential benefits of disseminating genetic information to male relatives of women undergoing BRCA1/2 testing. No significant financial relationships to disclose.
Active specific immunotherapy with a polyvalent cancer vaccine prolongs survival in AJCC stage IV melanoma
Authors: D. L. Morton, R. Essner, E. C. Hsueh, L. A. Wanek, L. J. Foshag, S. J. O'Day, R. K. Gupta, D. S. Hoon, G. Gammon
Journal: Journal of Clinical Oncology (2004)

2543 Background: The treatment of AJCC stage IV melanoma is inadequate; in a recent meta-analysis, median and 5-year survivals were 8.1 months and 2.3%. In phase II trials, we have evaluated the activity of active specific immunotherapy with a polyvalent therapeutic cancer vaccine (Canvaxin) and other immune adjuvants against stage IV melanoma. We compared the survival of vaccine-treated patients with the survival of comparable surgical and nonsurgical patients receiving nonvaccine therapies. Methods: Our study groups included all AJCC stage IV patients (N=1856) entered into our prospective database of 11,000 patients between 1/1/86 and 1/1/2001. Survival curves were estimated by Kaplan-Meier method, and statistical difference analyzed by log rank test and Cox regression according to the new AJCC staging system of Mla, Mlb and Mlc. Results: Although complete regression of evaluable disease was rare among vaccine patients, disease stabilization was common. Survival from initial stage IV diagnosis was prolonged almost twofold for the entire group of vaccine patients and for all vaccine-treated M1 subgroups (p = 0.001 - 0.05) except Mla (Table); 1-, 2-, 3- and 5-year survival rates were also significantly enhanced (p = 0.001). Toxicity of vaccine therapy was minimal: transient grade 1 or 2 fever, headaches, malaise and ulcerations at the injection sites. Skin-test and antibody responses to vaccine antigens were associated with enhanced survival. Conclusions: When compared with other postsurgical adjuvants and nonsurgical therapies, polyvalent vaccine immunotherapy significantly enhanced the survival of patients with resectable and nonresectable stage IV melanoma. This is the largest vaccine study yet reported, and the survivals are the longest yet observed in stage IV melanoma. These findings deserve further study in a multicenter randomized trial, which is currently underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CancerVax Corp. CancerVax Corp. CancerVax Corp.
Cancer in patients with HIV infection: A new epidemiology
Authors: S. Kodali, P. V. Kancharla, S. G. Naik, A. Sangal, C. Rathnasabapathy, K. Muhammad, B. Berger, Z. He, M. Kalavar
Journal: Journal of Clinical Oncology (2008)

11108 Background: Cancer is the leading cause of death in patients who have HIV infection. HAART has had a dramatic impact on life expectancy and the incidence of AIDS defining and Non AIDS defining cancer appears to be changing. Methods: We undertook a three-year retrospective review of Brookdale’s inpatients over 18 years, diagnosed with cancer, who were HIV positive. We correlated the CD4 count of the patients to the type of cancer. Results: Fifty charts were reviewed. Twenty-four patients were female, 26, male. Median age was 47 years (26 - 70). Twenty four (48%) patients had AIDS-defining and 26 (52%) had non-AIDS-defining cancers. Twelve (24%) had NHL. Ten had lung cancer, nine (18%) of them are non-small cell. Seven (14%) had KS, six, (12%) cervical carcinoma. Three (6%) had Hodgkin’s lymphoma. Two had anal cancer, two, breast cancer, three, nasopharyngeal, one, skin cancer, one, gastric cancer, one, hepatocellular and one, prostate cancer.CD4 counts were less than 200/ml in all patients with KS (mean 30/ml) and cervical cancer (mean 75/ml). All Hodgkin’s lymphoma patients had CD4’s over 200/ml (mean, 554). In NHL, ten of twelve (83%) had CD4’s less than 200/ml (mean, 137/ml). Of non-small cell lung cancer patients, six (67%) had CD4’s less than 200/ml (mean, 139/ml). The mean CD4 in patients with non-AIDS-defining malignancies was 263/ml (SD 255). Conclusions: In the era of HAART, HIV patients are at risk for non-HIV associated cancers, as that of AIDS-defining cancers and non-small cell cancers were the most common of non-HIV-associated cancers. Even with non-AIDS-defining malignancies, many patients present with low CD4’s. In this small study we cannot determine whether immunosuppression from HIV increases the risk of all cancers and will need larger multi institutional studies. Cancer Number of Cancers Number of patients with CD4 <200 Mean CD4 Count NHL 12 (24%) 10 (83%) 137 (122) Non small cell lung cancer 9 (18%) 6 (67%) 139 (SD 104) Kaposi’s sarcoma 7 (14%) 7 (100%) 30 (28) Cervical Cancer 6 (12%) 6 (100%) 75(29) Hodgkin’s Lymphoma 3 (6%) 0 554 (359) No significant financial relationships to disclose.
Acute myeloid leukemia (AML) in adolescents and young adults (AYA): The M. D. Anderson Cancer Center (MDACC) experience
Authors: N. Pemmaraju, H. Kantarjian, F. Ravandi, S. O'Brien, W. Wierda, D. Thomas, G. Garcia-Manero, G. Borthakur, S. Pierce, J. Cortes
Journal: Journal of Clinical Oncology (2009)

7051 Background: AML is a heterogeneous group of hematopoietic neoplasms demonstrating clonal proliferation of myeloid precursors and is typically a disease of older adults. Little is known about outcomes of AYA with AML. Methods: We retrospectively analyzed all patients (pts) with AML treated at MDACC from 1965 to 2008. Pts ages 16 to 21 years (yrs) were defined as AYA. Results: Among 3,934 adult AML pts treated during this period, 163 pts (4%) were AYA with median age of 19 yrs. This cohort included 27 (17%) pts with Core Binding Factor (CBF)-AML [inv(16), t(8:21)] and 19 pts (12%) with acute promyelocytic leukemia (APL). Among the other pts, 50% had diploid cytogenetics, 11% had 5 or 7 abnormalities, 39% had other cytogenetic changes. Antecedent hematologic disorders were present in 33 pts (20%). Among 20 evaluated pts, FLT3 internal tandem duplication (ITD) was present in 4 pts and FLT3 kinase domain mutation was found in 2 pts. Complete remission (CR) rates were 89% for CBF AML, 79% for APL, and 75% for all other pts. Median survival for the total cohort was 1.7 yrs with 36% alive at 3 yrs, and median CR duration of 1.3 yrs (30% CR at 3 yrs). Outcome is better for pts with CBF leukemia (3 yr survival 56%, sustained CR 49%) and APL (3 yr survival 51%, sustained CR 36%) compared to other AML (3 yr survival 28%, sustained CR 24%). CR rates have improved from 71% in 1965–1984, to 85% in 1985–1994, and 83% after 1994. Similarly, overall survival (OS) has increased during the same time periods (3-yr survival 18%, 44%, and 53%, respectively) together with CR duration (3 yr CR duration 21%, 32% and 39%, respectively) as early mortality has decreased (11%, 8%, and 4%, respectively). To compare outcomes of AYA with older adults, we focused on those with diploid cytogenetics.CR for pts ages 16–21 was 81%, with 3 yr survival of 46%; for ages 22–45, CR was 75% and 3 yr survival 36%; for ages 46–60 CR was 68% with 3 yr survival 28%; and for pts age greater than 60, CR was 54% with 3 yr survival of 22%. Conclusions: The outcome of AYA pts with AML is significantly better than for older adults with AML. Despite the advances in treatments over time, there is still significant room for improvement, particularly among those AYA with AML other than CBF and APL. Exploration of new treatment options is needed in this patient population. No significant financial relationships to disclose.
Incidence of EGFR and K-ras mutations in Japanese patients with mucinous bronchiolo-alveolar cell carcinoma of the lung
Authors: A. Hata, N. Katakami, R. Kaji, T. Nishimura, K. Tomii, K. Ishihara, Y. Imai, T. Komatsu, Y. Takahashi, S. Fujita
Journal: Journal of Clinical Oncology (2008)

14553 Background: In lung adenocarcinomas, especially Bronchiolo Alveolar Carcinomas (BACs), it has been reported that Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitors (EGFR-TKIs) have a high potency. But in fact, its efficacy differs among subtypes: in mucinous BACs (mBACs), it exhibits a poor effect compared to its performance in non-mucinous BACs (non-mBACs). One reason why is EGFR mutations are rare, and K-ras mutations are frequent, in mBACs relative to non-mBACs. Methods: From January 2004 to October 2007, 180 lung adenocarcinomas were diagnosed in pathological specimens after resections. 51 cases (28%) of BACs were classified. In these specimens, 17 mBACs (9%) and 34 non-mBACs (19%) were found. We extracted 41 cases of BACs (all mBACs and 24 cases of non-mBACs as control), and examined their EGFR mutations and K-ras mutations. We used the PNA-LNA PCR clump method to detect EGFR mutations, and K-ras mutations were explored by sequences after the enriched PCR method. Results: Only three EGFR mutations were found in 17 mBACs (18%), and 12 K-ras mutations were present (71%). By comparison, 14 EGFR mutations were detected in 24 non-mBACs (58%), and 11 K-ras mutations were identified (46%). Conclusions: In mBAC cases, the efficacy of EGFR-TKIs is poor, because EGFR mutation is rare and K-ras mutation is frequent. No significant financial relationships to disclose.