tbuckley/cabot-search huggingface dataset:
Yield from risk-based screening in adults treated for cancer in childhood.
Authors: M. M. Hudson, V. G. Nolan, K. K. Ness, G. T. Armstrong, D. M. Green, K. R. Krull, S. L. Spunt, M. Metzger, D. K. Srivastava, L. L. Robison
Journal: Journal of Clinical Oncology (2010)

9010 Background: To improve health outcomes after childhood cancer, all survivors should have risk-based care that includes tailored surveillance based on the previous cancer and cancer therapy. We determined the prevalence of previously undetected cancer-related toxicities in adults surviving childhood cancer evaluated by risk-based health screening. Methods: We evaluatedadult survivors of childhood cancer (≥ 18 years old, ≥ 10 years from diagnosis) participating in the ongoing St. Jude Lifetime (SJLIFE) study. To date, 93% of contacted survivors have agreed to participate. All underwent risk-based assessments appropriate for cancer diagnosis/treatment as recommended by the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. To direct risk-based assessment, chemotherapy cumulative doses, radiation fields/doses, and surgical procedures were abstracted from medical records. Results: As of08/29/2009, 626 SJLIFE participants completed risk-based assessments (56% female; 91% white, non-Hispanic). Median age was 7.6 years (range, 0-22.7) at diagnosis and 37.2 years (range, 20.5-62.5) at evaluation. Median time from diagnosis was 28.5 years (range, 12.3-47.4). Primary diagnoses comprised leukemia (n = 334), lymphoma (n = 143), and solid tumor (n = 149). Subclinical toxicity detected by risk-based screening is summarized below (Table). Conclusions: Risk-based screening approximately 3 decades after diagnosis of childhood cancer detected previously undiagnosed cancer-related toxicity in a substantial proportion of survivors. Risk-based screening identifies individuals who may be candidates for interventions designed to slow or prevent progression of subclinical disease. Organ system No (%) at risk No (%) diagnosed before screening No (%) new events detected by screening Cardiovascular 500 51 (10) 246 (49) Endocrine 412 130 (32) 33 (8) Hepatic 439 1 (<1) 1 (<1) Infectious 443 52 (12) 5 (1) Musculoskeletal 418 42 (10) 127 (30) Neurocognitive measures 381 155 (41) 192 (52) Neurologic 545 31 (6) 138 (25) Neurosensory 420 62 (15) 194 (46) Pulmonary 164 81 (49) 52 (32) Reproductive 484 133 (27) 138 (29) Urinary tract 590 32 (5) 24 (4) Second malignancy 626 99 (16) 20 (3) No significant financial relationships to disclose.
Predictive values of intratumoral microvascular density (MVD) in the patients (pts) with advanced NSCLC and metastatic colorectal cancer (mCRC) receiving chemotherapy plus bevacizumab
Authors: L. Zhang, W. Jiang, Y. Zhang, R. Xu, C. Qian, J. H. Resau, K. VandenBeldt
Journal: Journal of Clinical Oncology (2009)

e14618 Background: The using of bevacizumab (VEGFR inhibitor) combined with chemotherapy represents a most noticeable recent advance in clinical oncology for significantly improving pts’ survival in several tumor types. There is an unmet need for seeking biomarker(s) to predict the treatment response of bevacizumab and identify the pts sensitive to the treatment. Our study was designed to investigate the predictive value of intratumoral MVD in NSCLC and mCRC pts treated with bevacizumab. Method: Sixteen NSCLC (stage IIIB/IV) and 15 mCRC pts who underwent chemotherapy (paclitaxel+carbo for NSCLC and IFL for CRC, respectively) combined with Bevacizumab were included into this study. The paraffin-embedded tumor samples (13/16 NSCLC and all CRC samples were collected from primary tumor) were sectioned and stained immunohistochemically for blood vessel markers (CD34 and CD31) to identify the characteristics of intratumoral vasculature. A computerized image analysis program was used to quantitatively calculate the intratumoral MVD (Yao et al., Clin Cancer Res 2007). Treatment response was evaluated by computed tomography scanning. Results: Two types of blood vessel, undifferentiated (CD31+/CD34-) and differentiated (CD34+), were identified. For the 16 NSCLC pts, a positive correlation was found between the largest tumor shrinkage percentage (evaluate in the primary tumors and metastases) and the total (CD31+) MVD as well as the undifferentiated (CD31+/CD34-) MVD, with Spearman's correlation coefficients equaled to 0.567 (p=0.022) and 0.576 (p=0.019), respectively. However, no significant correlation between tumor shrinkage and MVD was found in CRC pts, in which the treatment response was evaluated in metastatic lesions while the MVD was calculated in primary tumor. Conclusion: This exploratory analysis suggests higher total vessel and undifferentiated vessel MVD appeared to be predictive of bevacizumab treatment advantage for advance NSCLC pts.Our study also indicated that the MVD of primary lesions did not correlate with the treatment response of metastatic lesions in CRC pts. Further studies are needed to verify the predictive role of MVD in the treatment of bevacizumab in NSCLC. [Table: see text]
Is tamoxifen prevention in younger women underutilized? Analysis of competing causes of mortality
Authors: J. Ragaz, J. J. Spinelli, A. Coldman, C. Mihalcioiu
Journal: Journal of Clinical Oncology (2006)

647 Background: Our past work on Tamoxifen impacting overall mortality outcome among survivors of the 1 st breast cancer (JCO, 1998, 16:2018–24) introduced methodology permitting analyses of competing cause mortality, adjustable as new data emerge. This analysis estimates Tamoxifen impact on four conditions among BrCa survivors known to be affected by Tamoxifen, i.e. contralateral breast cancer; uterine cancer, cardiovascular (CVS) mortality, and thromboembolism (TE). Updated RR rates of Tamoxifen impacting the four conditions were obtained from recent literature (Lancet, 2005, 365:1687–1717; JNCI,2005, 97:1652–62; 97:1609–10). Methods: The effect of Tamoxifen was calculated by applying Relative Risk Rates (RR) to the respective underlying Canadian age-specific mortality figures, separately for each condition. The final mortality impact was the “net mortality”, defined as differences of deaths, from each condition, between 1,000 Tamoxifen users vs 1,000 non-users (Dif N/1,000), expressed for ages &lt;50 and &gt;50. (i.e sum of avoidances [-] vs hazards[+]) Results: see Table below. Conclusion: Our results show a favorable Tamoxifen impact on overall mortality, particularly evident for women age &lt;50, in whom the breast cancer mortality reduction significantly outweighs the hazards. These data are applicable to Tamoxifen prevention in population-women who are at high risk for BrCa. Their outcome profiles affected by Tamoxifen mirror those of the survivors of the 1 st BrCa. While for women &gt;50, other chemoprevention alternatives exist (i.e. trials of Aromatase Inhibitors), for younger women no chemoprevention trials are presently in existence. Our data indicate that in those, routine use of Tamoxifen may save substantial numbers of lives. [Table: see text] No significant financial relationships to disclose.
Phase II trial of imatinib mesylate and hydroxyurea for adults with recurrent/progressive low-grade glioma
Authors: D. A. Bota, A. Desjardins, J. A. Quinn, J. N. Rich, J. J. Vredenburgh, S. Sathornsumetee, K. Goli, A. Salvado, H. S. Friedman, D. A. Reardon
Journal: Journal of Clinical Oncology (2007)

2053 Background: We evaluated the combination of imatinib mesylate and hydroxyurea in recurrent/progressive low-grade gliomas (LGG) following the encouraging response of this combination demonstrated among adults with recurrent malignant glioma. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky = 60% and adequate organ function. Imatinib plus hydroxyurea were given on a continuous oral daily schedule for 28 day cycles; imatinib was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of hydroxyurea. Patients were evaluated every other month with physical and MRI examinations. Results: Twenty-seven patients with recurrent or progressive LGG have enrolled including 17 with astrocytoma and 10 with oligodendroglioma. Eleven (40.7%) are on EIAED. Median age was 42 years (range 24–66 years). 26% of patients had received prior therapy other than surgery (XRT, n=2; chemotherapy, n=5). The most frequent toxicities possibly related to the study regimen were fatigue (grade 2, n=5; grade 3, n=1), neutropenia (grade 2, n=1; grade 3, n=2), anemia (grade 2, n=2), rash (grade 2, n=2), nausea (grade 3, n=1), anorexia (grade 2, n=1), and AST elevation (grade 2, n=1). There were no grade 4 or 5 treatment-related toxicities. Among patients evaluable for response, 17 (85%) achieved stable disease and 3 (15%) had progression. Twenty patients continue on study having received 2–16 months of therapy. Additional accrual and follow-up is ongoing. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG. [Table: see text]
A multicenter, randomized, phase III study comparing paclitaxel/carboplatin (PC) versus topotecan/paclitaxel/carboplatin (TPC) in patients with stage III (residual tumor &gt; 1 cm after primary surgery) and IV ovarian cancer (OC)
Authors: G. Scarfone, G. Scambia, F. Raspagliesi, G. Mangili, S. Danese, M. Presti, F. Petruzzelli, B. Costa, G. Bolis
Journal: Journal of Clinical Oncology (2006)

5003 Background: Despite treatment with standard first-line PC, survival rates of patients with OC is disappointing, especially in patients suboptimally debulked. In this phase III, open-label, randomised, parallel-arm study topotecan, a non cross-resistant topoisomerase I inhibitor was added to the standard platinum-taxane doublet in order to improve survival and progression-free interval compared to PC alone. Methods: 326 ITT patients with FIGO stage III (residual tumor &gt; 1 cm) and IV OC were randomly allocated to receive either carboplatin AUC 5 and paclitaxel 175 mg/sqm d1q21 (arm A; 170 pts) or topotecan 1 mg/sqm dd1–3q21 + carboplatin AUC 5 and paclitaxel 175 mg/sqm d3q21 (arm B, 156 pts) for 6 cycles. Primary endpoint was the 3-year survival rate with 350 patients originally planned to show an increase in 3-year survival from 20 in arm A to 35% in arm B with 80% power and alfa = 0.05. Results: 81.8% and 77.6% of patients in arm A and B respectively completed the 6 cycles planned. The 2 arms were well balanced for demography, tumor staging and histology except for an excess of serous histotype in the arm B (68.2% vs 75%). Best overall response was CR/PR in 51.5%/33.7% (ORR 85.2%) in arm A and 57.8%/36.3% (ORR 92.5%) in arm B (p = 0.586 with χ 2 test, NS). Median time to progression (TTP) was 70.4 and 71.8 weeks in arm A and B respectively (p = 0.5058 with Wilcoxon test, NS). Most common G3/4 hematological toxicity was neutropenia (7.1% and 13.2% of courses and 23.5% and 39.7% of pts in arm A and B) and most common non-hematological toxicities were alopecia (78.2% and 72.4% in arm A and B) and nausea/vomiting (43.5% and 50.5% in arm A and B). 13.9% and 15.5% of courses were delayed and 2.1%/2.4% and 7.2%/6.2% of carboplatin/paclitaxel doses reduced for toxicity in arm A and B respectively. 9.4% and 23.3% of courses required transfusions in arm A and B respectively. Conclusions: The addition of topotecan to standard PC primary chemotherapy does not increase RR and TTP in stage III (residual tumor &gt; 1 cm) or IV OC compared to PC alone. The TPC regimen was well tolerated with a minority of patients experiencing G3/4 hematological toxicity. Study funded by GlaxoSmithKline. No significant financial relationships to disclose.
Temozolomide (TMZ) in radio-chemotherapy combined schedule for treatment of newly-diagnosed high-grade gliomas (HGG)
Authors: P. Montemaggi, P. Guerrieri, G. Mortellaro, G. Composto, S. Russo, D. Piazza, S. Rizzo, I. Carreca
Journal: Journal of Clinical Oncology (2005)

1578 Background: Temozolomide (TMZ) is an oral alkylating agent known to cross the blood-brain barrier with efficacy against HGG and a favourable safety profile compared to conventional chemotherapy agents, such as nitrosoureas. The aim of this study was to determine if the combined strategy of this drug with radiation therapy (RT) is associated with an improved overall survival (OS) of patients with histologically confirmed glioblastoma multiforme (GBM) and grade III anaplastic astrocytoma (AA) and to evaluate toxicity. Methods: Forty patients (28 males and 12 females; median age, 52 years; age range, 35–65 years) were enrolled in this trial. TMZ was administered starting the first day of RT at a dose of 75 mg/m2 daily. RT parameters were a total dose of 66 Gy delivered in single 2 Gy daily fractions over 6 ½ weeks using the shrinking field technique. Concomitant TMZ with RT was followed by TMZ alone at a dose of 250 mg/m2 daily for five days repeated every 28 days for 6 cycles. Tumor response was evaluated by [(18)F]fluorodeoxyglucose(FDG)-PET imaging before and after treatment to detect local recurrences. Median follow-up was 26 months [range 6–36 months (for patients alive)]. Results: Fifteen patients had a partial response (PR), twenty patients had a stable disease (SD) and five had a progression disease (PD). Follow-up: median OS was 20 months (range 6–28 months). Ten out of forty patients showed an increased uptake of FDG and were boosted with fractionated stereotactic dynamic arc intensity-modulated radiation therapy (IMRT). The total radiation dose was 30 Gy delivered in single 3 Gy daily fractions. General haematological toxicity was between mild and moderate (only five patients experienced grade 3–4 thrombocytopenia) except for one severe pancytopenia. Conclusions: Authors conclude that this radio-chemotherapy combined schedule is well tolerated except for haematological disorders. Data regarding OS seem to be encouraging even if large randomized trials are necessary to further validate early outcomes. No significant financial relationships to disclose.
MEDI-551, an anti-CD19 antibody active in chronic lymphocytic leukemia (CLL) patients previously treated with rituximab.
Authors: Mehdi Hamadani, Andres Forero, Thomas J. Kipps, Michelle A. Fanale, Antonio Cuneo, Jaime Perez de Oteyza, Douglas Gladstone, Trishna Goswami, Ramy A. Ibrahim, Meina Liang, Steven Eck, Nairouz Elgeioushi, Ronald Herbst, Bruce D. Cheson
Journal: Journal of Clinical Oncology (2013)

7045 Background: Anti-CD20 mAb therapy has provided survival advantage to patients (pts) with CLL; but pts invariably relapse after anti-CD20 therapy and new approaches are needed. The CLL cells of most pts express CD19, which are upregulated following anti-CD20 therapy. MEDI-551, an affinity-optimized anti-CD19 antibody, destroys malignant cells by Ab-dependent cellular cytotoxicity (ADCC) once bound to CD19. Methods: The activity and toxicity of single-agent MEDI-551 in CLL pts with prior rituximab administration was assessed in a phase 1/2, open-label, dose-escalation and expansion study (NCT00983619). Response was assessed using the 2008 Intl Working Group criteria. B-cell depletion was assessed with flow cytometry and confirmed with biomarker analyses (BAFF). Safety assessments included laboratory parameters and adverse events (AEs and serious AEs [SAEs]). Results: Of 91 pts with refractory B-cell malignancies included in the study, 26 had CLL. CLL pts had received a median of 6 prior therapies: 89% with chemotherapy, 27% with single-agent biologics. Within 3 cycles of MEDI-551 (3 mos), &gt;60% of assessable pts achieved CD20 + B-cell depletion to &lt;20 cell/uL. Decreases in circulating CD20 + and CD22 + B cells were associated with concomitant increases in serum BAFF concentrations. Of 20 pts evaluable for response, 4 achieved partial response and 13 had stable disease. Commonly reported AEs were generally grade 1/2 and included infusion reactions (62%), nausea (23%), pyrexia (23%), and neutropenia (23%). Six SAEs were noted in 3 pts: 1 had infusion reaction and general health deterioration, another had subarachnoid hemorrhage (SAH), and a third had dyspnea, pyrexia, and back pain. Only infusion reaction was considered treatment related. Two treatment-unrelated events of general health deterioration and SAH resulted in death. Conclusions: Single-agent activity with a manageable toxicity profile was seen in CLL pts treated in this phase 1/2 study of MEDI-551. An ongoing phase 2 study of MEDI-551 in combination with bendamustine in relapsed CLL patients (NCT01466153) is evaluating clinical response to MEDI-551 and chemotherapy. This study was sponsored by MedImmune, LLC.
Risk of having BRCA mutations in women with triple-negative breast cancer: A systematic review and meta-analysis.
Authors: N. M. Tun, G. M. Villani, K. Ong
Journal: Journal of Clinical Oncology (2011)

160 Background: Increased prevalence of BRCA1 mutations (BRCA1) has been associated with the occurrence of triple-negative breast cancer (TNBC) (estrogen receptor [ER]- and progesterone receptor [PR]-negative, HER2-negative) in independent clinical studies. However, BRCA2 mutation (BRCA2) has not been found to overrepresent in women with TNBC. We have performed a meta-analysis of these studies to provide further statistical evidence of the association between BRCA positivity and TNBC. Methods: A Medline search of the MeSH terms “BRCA”, “triple”, and “negative” yielded 37 articles. A search of ASCO abstracts yielded 18 relevant articles. Random effects model was used for analysis due to heterogeneity among the proportions of included studies (Cochran’s Q = 18.52 and 15.18, tau 2 = 0.61 and 1.29, I 2 = 73% and 80% for BRCA1 and BRCA2 respectively). Mantel-Haenszel method was applied to calculate the pooled event-based odds ratio (OR) with 95% confidence interval (CI). Results: 6 studies including 1,602 BC patients were eligible for analysis of BRCA1 and 4 studies including 1297 BC patients for BRCA2. 172 patients with BRCA1 mutations and 79 patients with BRCA2 mutations were analyzed. Among these 6 studies, 1 included Ashkenazi Jewish women exclusively and 1 included only women of Chinese descent. The overall prevalence of BRCA1 was 10.05% (172 out of 1,602), and for TNBC patients 21.94% (95 out of 433) with an odds ratio of 5.90 (CI: 2.75, 12.66, p &lt; 0.00001). TNBC was not a risk for BRCA2 (OR = 0.67, CI: 0.19, 2.39, p = 0.53). Chinese women with TNBC did not have an elevated risk of BRCA1 (OR = 0.94, CI: 0.24, 3.66) in contrast to Jewish women with TNBC who had the highest risk of BRCA1 among the populations studied (OR = 21.79, CI: 9.03, 52.55). Conclusions: Women with TNBC carry a significantly high risk of having BRCA1 but not BRCA2 mutations. We recommend genetic testing for BRCA1 mutations in women with TNBC especially in Ashkenazi Jewish population. Further studies on Chinese population are needed to further establish the relationship between TNBC and BRCA1 mutations in this cohort.
Abstract 14573: Cardiac Developmental Roadmap Predicts Cardiogenic Outcome of Pluripotent Stem Cells
Authors: Almudena Martinez Fernandez, Xing Li, Katherine A Harthes, Andre Terzic, Timothy J Nelson
Journal: Circulation (2012)

Rationale: Cardiogenic development is a complex process giving rise to an integrated, multi-lineage cardiac tissue. Interrogation of individual genes has provided the backbone for cardiac developme...
A phase II trial of imatinib in patients with advanced carcinoid tumor
Authors: K. Carr, J. C. Yao, A. Rashid, S.-C. Yeung, J. Szklaruk, J. Baker, J.-N. Vauthey, S. Curley, L. Ellis, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

4124 Background: Effective systemic therapy options for carcinoid tumors are lacking. Carcinoid tumors co-express PDGF and PDGFR, a receptor/ligand system important in cell growth and survival. A phase II trial was conducted to assess the response rate and safety profile of PDGFR inhibitor, imatinib (Gleevec ™), at a dose of 400 mg PO BID in patients with advanced carcinoid tumors. Methods: Previously treated or untreated patients with advanced carcinoid tumors with adequate organ and bone marrow function were included. Response was evaluated every 12 weeks by CT or MRI. Results: 15 men and 12 women with a median age of 60 (22–74) enrolled. 21 patients received concurrent octreotide. 10, 6, 3 and 2 patients received prior chemotherapy, hepatic artery embolization, interferon, and radiation, respectively. Median number of weeks on study was 16 (range, 12–78+). By RECIST criteria, 1 patient, receiving concurrent octreotide, had a radiologic PR (remains on study after 1.5 years), 17 had SD, and 9 with PD. Among 14 patients with PD at entry, 8 patients remained progression free for at least 12 weeks (range, 18–52+). 4 patients had > 50% reduction in markers (chromogranin, 5-HIAA, pancreatic polypeptide). Median PFS duration is 24 weeks (range, 12–68+). PFS duration was significantly better in patients receiving concurrent octreotide (14 weeks vs 38 weeks; P=0.05). 1-year OS rate is 88%. There was no correlation between plasma VEGF and bFGF, CT flow studies and patient outcome. Grade 3–4 toxicities included fatigue (7), hypophosphatemia (5), diarrhea (3), fluid retention (3), nausea (2), granulocytopenia (2), hypokalemia (2), rash (1), anorexia (1), thrombocytopenia (1), hyperglycemia (1), and hyperbilirubinemia (1). Conclusions: Our data suggest a modest level of biologic effect of imatinib in carcinoid, therefore, further development of imatinib in conjunction with other agents may be warranted. Supported by a grant from Novartis. No significant financial relationships to disclose.