tbuckley/cabot-search huggingface dataset:
Arsenic trioxide for treatment of myelodysplastic syndrome: An experience from India
Authors: A. Mukhopadhyay Sr., S. Das, S. Dey, R. Choudhury, R. Ahmed, P. Gupta, A. Dhara, S. Chakraborty, B. Halder, S. Mukhopadhyay
Journal: Journal of Clinical Oncology (2006)

13156 Background: Myelodysplastic Syndrome (MDS) is a heterogeneous group of clonal diseases of the haematopoietic stem cells. The hallmark of the disease is ineffective haematopoiesis characterized by dysplasia with incomplete maturation and progressive increase in the percentage of myeloblast. No standard treatment is currently available for MDS. The early clinical experience has confirmed the activity of arsenic trioxide in MDS. The drug is able to induce differentiation and apoptosis and to inhibit cell proliferation or angiogenesis. It has the potential to be active in tumour models in MDS. The preliminary result of ongoing studies conducted in patients with MDS suggests that arsenic trioxide produces haematological improvement including durable transfusion independence in 30% of patients. The aim of our study was to see the response of MDS with arsenic trioxide and to see the toxicity profile of arsenic trioxide in Asian Indian population. Methods: During period from July 2005 to December 2005 we selected consecutive 10 patients of MDS in Refractory Anaemia, Refractory anaemia with ringed sideroblasts, Refractory anaemia with blast excess, Refractory anaemia with blast excess in transformations and chronic myelo monocytic leukemia phases. All patients had performance status more than 60%, some karyotypic abnormalities &amp; in cytopenic phase. Median age of the patients 65 years (range 42 to 70 years). All patients were treated with arsenic trioxide 10mg (Alkem/India) daily for 2 hours infusion 28 days. In 15 days interval 3 courses were repeated. Response assessments were done by haematological, cytogenetic &amp; quality of life assessment. All patients were evaluated after 3 courses of arsenic trioxide. Result: Sixty percent (6 patients) patients had shown major haematological response, forty percent minor &amp; twenty percent has major cytogenetic response. Twenty percent of the patients has disease progression where as 20% has stable disease. The only mild adverse effects were seen in forms of nausea, vomiting, diarrhea, abdominal pain &amp; dermatitis in 30% of patients. Only one patient (10%) had QT prolongation in ECG. Conclusion: We concluded that arsenic trioxide is very useful drug in myelodysplastic syndrome. It is also well tolerated in Asian Indian Population. No significant financial relationships to disclose.
Single-fraction image-guided extracranial radiosurgery for recurrent and metastatic abdominal cancers: Short-term local control, metabolic response, and toxicity
Authors: C. L. Perkins, J. S. Kauh, C. A. Staley, J. Landry
Journal: Journal of Clinical Oncology (2008)

15597 Background: Extracranial radiosurgery (ECRS) is a novel treatment for inoperable recurrent or metastatic abdominal cancers. However, local control, metabolic response, and acute toxicity remain undefined. We therefore analyzed these endpoints in patients treated with single- fraction image-guided ECRS at Emory University. Methods: 10 patients with recurrent or metastatic inoperable abdominal cancers (12 sites) were treated with single-fraction ECRS using a Varian linear accelerator between 08/2006 and 07/2007. In 8 patients pre-treatment PET/CT was used to delineate the target volume. Image-guidance was provided by implanted fiducial markers and on-board imaging in 9 patients, and with cone-beam CT in 1 patient. 4 Patients were treated with respiratory gating. The median single-fraction dose delivered was 18 Gy. Each patient was assessed at 1 week, 1 month, and 3 months after radiosurgery for toxicity, and at approximately 1 month and 3 months with PET/CT for metabolic tumor response. Partial response was defined as a reduction in size of ≥ 10% on CT and a decrease in maximum SUV of ≥ 15% on PET. Complete response was defined as complete resolution on CT, and a reduction of SUV to background levels on PET. Results: The median follow-up was 4.2 months (range 1.4–9.1 months). Local control was achieved in 83.3% of all sites (8 patients). 2 patients (2 sites, 16.7%) showed progression at last follow-up. 2 patients (2 sites, 16.7%) showed stable disease, 5 patients (5 sites, 41.7%) showed a partial response, and 3 patients (3 sites, 25%) showed a complete response. 75% of sites showing an early response on the 1-month PET/CT maintained local control at 3 months. At 1 week, toxicity was grade 1 GI 40%, and grade 2 GI 20%. At 1 month follow-up, grade 1 GI toxicity was seen in 30%, and grade 2 GI toxicity was seen in 30%. Conclusions: Single-fraction image-guided ECRS for recurrent or metastatic abdominal cancers is safe and effective in the short term. 3-month local control was excellent, and was predicted by an early metabolic response as seen on PET/CT. Acute side effects were mild, with no patients receiving grade 3 or greater toxicity. Dose escalation and long-term studies are warranted for this treatment approach. No significant financial relationships to disclose.
Epidemiological trends in renal cell carcinoma (RCC) in the cytokine (CYT) and targeted therapy (TT) eras: A registry analysis of 28,252 patients (pts).
Authors: D. W. Shek, M. Brown, C. Pan, P. Lara
Journal: Journal of Clinical Oncology (2010)

4598 Background: Randomized trials of TT have shown significant improvement in RCC pt outcomes, leading to the approval of 6 new agents since 2004. It is uncertain whether this improvement is confined to highly selected pt cohorts in clinical trials or if this benefit has already translated to the broader RCC population. To explore this, we analyzed a large RCC pt registry for epidemiologic trends, comparing the CYT (1998-2003) and TT (2004-2007) eras. Methods: Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, were used. We retrospectively analyzed 28,252 RCC pts diagnosed between ’98-’07. Inter-era differences in clinical variables including year of diagnosis, histology, age, sex, race, stage, nephrectomy (Nx) status, overall (OS) and cause-specific (CSS) survival were assessed. Results: RCC frequency increased from 7.55% to 12.46%. SEER stage at diagnosis was localized in 64.42%, regional in 17.25%, and distant in 16.5%. Nx rate for pts with distant stage was 44%. Non-clear cell histologies increased (10.97% to 19.73%, p<0.001). Inter-era comparisons are shown in the Table. Conclusions: In this initial analysis of a large RCC registry, OS and CSS have not appreciably increased in the TT versus CYT era. These preliminary results suggest that the OS benefit from TT has not yet translated into the general RCC pt population. However, longer follow-up for pts in the TT era is necessary for a more robust comparison of long term OS. Multivariate OS analysis of the CCR database is ongoing. Supported by the Egan Family Fund. Variable Cytokine era (1998-2003)N = 14,956 Targeted therapy era (2004-2007)N = 13,296 Age, median in yrs 63 63 Clear cell histology (n, %) 13,316 (89.03) 10,673 (80.27) White race 9,900 (35.4) 8,209 (29.35) Stage (localized) 9,193 (61.47) 9,008 (67.75) Stage (regional) 2,732 (18.27) 2,141 (16.1) Stage (distant) 2,684 (17.95) 1,977 (14.87) Male sex 9,614 (64.28) 8,598 (64.67) Nephrectomy—yes (all pts) 12,647 (84.56) 11,389 (85.66) 3 yr survival, crude (all pts)* 68% 75% 3 yr survival (cause-specific)* 81% 81% 3 yr survival (cause-specific), clear cell histology* 77% 83% 3 yr survival (cause-specific), distant stage* 19.6% 20.5% * Estimated No significant financial relationships to disclose.
Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): Results from NCCTG Intergroup Phase III Trial N0147.
Authors: S. R. Alberts, D. J. Sargent, T. C. Smyrk, A. F. Shields, E. Chan, R. M. Goldberg, S. Gill, M. S. Kahlenberg, S. N. Thibodeau, S. Nair
Journal: Journal of Clinical Oncology (2010)

CRA3507 Background: FOLFOX is standard adjuvant therapy for stage III CC. Adding Cmab to FOLFOX benefits pts with metastatic CC WT KRAS tumors. N0147 assessed the potential benefit of Cmab added to FOLFOX. Methods: 21-56 days following resection and informed consent, KRAS status was centrally determined. Pts with wtKRAS CC were randomized to 12 biweekly cycles of oxaliplatin 85 mg/m 2 d1, with leucovorin 400 mg/m 2 , 5FU 400 mg/m 2 bolus IV, then 46-hr IV 5FU 2,400 mg/m 2 on d1-2 (mFOLFOX6), without (arm A) or with Cmab (arm D) 250 mg/m 2 d1&amp;8, with Cmab at 400 mg/m 2 , cycle 1, d1. Primary endpoint was 3-yr disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Planned accrual of 2,070 wtKRAS pts provided 90% power to detect hazard ratio (HR) of 1.33 with 2-sided α=0.05; with interim analyses after 25%, 50%, and 75% of planned events. Results: 1,760 wtKRAS pts (Arm A-858, Arm D-902) were enrolled at the time of closure; median follow-up on 1,624 pts is 15.9 months. Trial closed to accrual when preplanned interim analysis after 50% of planned events demonstrated no benefit to addition of Cmab. 3-yr DFS favored FOLFOX alone (HR 1.18, 95% CI 0.92-1.52; p=0.33). No benefit of Cmab was observed in any subgroups assessed. Any grade ≥ 3 AE, diarrhea, and failure to complete 12 cycles was significantly increased in arm D. Increased toxicity and greater differences in all outcomes were observed in pts aged ≥ 70 ( Table ). Conclusions: In this randomized phase III trial the addition of Cmab to mFOLFOX6 was of no benefit for pts with resected stage III wtKRAS CC. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]
A phase II study of capecitabine, oxaliplatin, and bevacizumab for metastatic or unresectable neuroendocrine tumors: Preliminary results
Authors: P. L. Kunz, T. Kuo, H. L. Kaiser, J. A. Norton, T. A. Longacre, J. M. Ford, G. A. Fisher
Journal: Journal of Clinical Oncology (2008)

15502 Background: Neuroendocrine tumors are a rare and heterogeneous class of neoplasms. Chemotherapy has low response rates with short duration while at the same time incurring significant toxicity. These tumors frequently metastasize to the liver and have a classic hypervascular appearance that is distinct from most other types of cancers, making this class of tumors an interesting target for angiogenesis inhibition. Early data suggest that single-agent bevacizumab for advanced carcinoid tumors inhibits tumor blood flow and increases progression- free survival (Yao et al, Proc ASCO 2005). Here we report preliminary data from a phase II study using capecitabine, oxaliplatin and bevacizumab in patients with metastatic or unresectable neuroendocrine tumors. Methods: Eligible patients had biopsy proven metastatic or unresectable neuroendocrine tumors, an ECOG performance status ≤ 2, and no prior oxaliplatin or angiogenesis inhibitors. Treatment consisted of four cycles of bevacizumab 7.5 mg/kg iv and oxaliplatin 130 mg/m2 iv on day 1 and capecitabine 850 mg/m2 twice daily by mouth on days 1–14 on a 21-day cycle. Patients with stable disease (SD) or partial response (PR) were allowed to continue therapy with bevacizumab with or without capecitabine. The primary endpoints were progression free survival (PFS) and toxicity. Results: Thirteen patients of a planned 37 have been enrolled to date. Ten of the 13 patients had radiographic evidence of progressive disease prior to study entry. Four patients achieved a PR (duration in weeks: 33, 27+, 27+, 27+) and 6 had SD (duration in weeks: 45+, 18, 48+, 48+, 12, 27+). One withdrew from treatment before completing the first cycle while two others are not yet evaluable for response. Overall, the treatment was well-tolerated with hematologic, gastrointestinal, neurologic and vascular toxicities as expected with this regimen. Of interest, a transient increase in pain in sites of disease was documented in 6 of 13 patients. Conclusions: The combination of capecitabine, oxaliplatin and bevacizumab in metastatic or unresectable neuroendocrine tumors is well tolerated. Early efficacy results are promising. Accrual to the study continues, with updated results to be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology
Perioperative chemotherapy treatment patterns in stage III transitional cell carcinoma (TCC) (1998–2003): A report from the National Cancer Data Base (NCDB)
Authors: K. A. David, D. M. Nanus, M. I. Milowsky, J. Ritchey, A. Stewart, P. R. Carroll
Journal: Journal of Clinical Oncology (2006)

4540 Background: Studies have demonstrated benefits of perioperative chemotherapy in locally advanced TCC. We reviewed chemotherapy treatment patterns in patients with stage III TCC of the bladder and upper urinary tract (UUT) between 1998–2003 to investigate the use of perioperative chemotherapy. Methods: The NCDB collects data on approximately 75% of all newly diagnosed cancer cases annually in the U.S. We queried for all treatments in male and female (≥18 years old) TCC cases diagnosed between 1998 and 2003. Cancer stage (1998–2002) was forward converted to AJCC 6 th edition. A total of 223,050 bladder and 11,625 UUT TCC cases were found. Results: Treatment patterns were analyzed in 11,328 patients with stage III bladder TCC and 1,840 patients with stage III UUT TCC, representing 5.0% and 15.8% of all cases, respectively (Table). Satisfactory follow-up was available for approximately 51% of patients. 5.4% (bladder) and 3.5% (UUT) of patients received pre-operative or adjuvant (within 4 mos of surgery) chemotherapy. No significant difference was seen comparing 1998 and 2003 perioperative chemotherapy use for bladder or UUT cancers. Conclusions: No increase in perioperative chemotherapy use occurred over the 5-year period (1998–2003), suggesting chemotherapy is underutilized in the management of surgically resectable stage III TCC of the bladder or UUT. This may reflect a delay in implementing the results of randomized trials recently reported or a low incidence of referral by urologists for perioperative chemotherapy. Further follow-up will determine if this pattern changes over the next 5 years. [Table: see text] No significant financial relationships to disclose.
Adrenomedullin and its receptors expression in renal tumors
Authors: J. Deville, S. Salas, C. Bartoli, C. Dupuis, F. Duffaud, G. Sebahoun, D. Figarella-Branger, L. Ouafik, P. Martin, L. Daniel
Journal: Journal of Clinical Oncology (2007)

10568 Background: Adrenomedullin (AM) is a 52 amino acid peptide that has an important role on tumor cell proliferation and neoangiogenesis through its receptors CRLR/RAMP2 and CRLR/RAMP3. AM gene expression is stimulated by Hypoxia Inductible Factor-1 (HIF- 1) and 60–80% of the human conventional renal carcinomas (cRCC) display mutations in the tumor suppressor protein von Hippel-Lindau, which leads to constitutively elevated HIF-1. Methods: Tumors and non-malignant kidney tissues were obtained from patients who underwent unilateral nephrectomy. We studied VEGFA, AM and its receptors expression by quantitative RT-PCR in 62 frozen renal tumors including: 40 cRCC; 5 cRCC metastasis; 5 chromophobe carcinomas; 5 Papillary carcinomas; 2 oncocytomas; 2 collecting duct carcinomas; 2 normal adjacent renal tissue; 1 unclassified renal tumor. AM and AM-receptors expression was studied in 42 paraffin-embedded renal tumors by immunohistochemistry using rabbit anti-AM, anti-CRLR, anti-RAMP2 and anti-RAMP3 polyclonal antibodies. Effects of these anti AM or anti AM- receptors antibodies on cell proliferation were examined in vitro on BIZ cell line (cRCC cells). Results: VEGFA, AM and AM-receptors genes were overexpressed in cRCC compared to other renal tumors (Except AM gene in chromophobe carcinoma). Their expressions were independent of classical prognostic factors (such as Fuhrman Grade and pT status). In cRCC, there was a strong positive correlation between VEGF-A gene expression and AM (r=0.7; p=0.01) and AM-receptors genes expressions (RAMP2 r=0.61; p= 0.01 and RAMP3 r=0.58; p= 0.01). Immunohistochemistry confirmed a tumor expression of CRLR, RAMP2 and AM in more than 80% cRCC. RAMP3 was expressed by inflammatory cells but not by tumoral cells. The cell proliferation assay showed a significant inhibition of BIZ cell proliferation by AM antibody or AM-receptors antibodies. Conclusion: AM and its receptor CRLR/RAMP2 are overexpressed in cRCC. In vitro cell proliferation assay results support that AM inhibition may suppress cRCC growth, independently of potential antiangiogenic effects. Further studies on animal models are needed but AM pathway may be a potential therapeutic target in cRCC. No significant financial relationships to disclose.
Risk for death from prostate cancer predicted from complete family history of lethal prostate cancer (LPC).
Authors: Frederick S. Albright, Neeraj Agarwal, William Thomas Lowrance, Robert A Stephenson, Anitha Alex, Lisa A Cannon-Albright
Journal: Journal of Clinical Oncology (2015)

175 Background: There are few published reports of relative risk (RR) for LPC based on family history of prostate cancer (PC) lethality. This study provides LPC RR using complete LPC family history data obtained from a statewide Cancer Registry linked to a genealogy database. Methods: The Utah Population Data Base (UPDB), which includes a statewide SEER cancer registry, includes 1,192,768 individuals with at least 12 of their 14 immediate ancestors. All males (probands) with specific LPC constellations were identified in the UPDB, and the observed number of LPC cases among these probands was compared to the expected number of LPC cases using internal cohort-specific rates from Utah death certificates including all deceased males with no 1st, 2nd, or 3rd degree relatives with LPC. LPC Family history was estimated for 1st degree to 3rd degree relatives for: number of LPC relatives affected, paternal versus maternal family history, and age at first PC diagnosis. Results: 3,921 individuals in UPDB were diagnosed with histologically confirmed PC, and had a Utah death certificate indicating PC as a cause of death and were designated LPC. The RR for LPC was significantly elevated with each additional first-degree relative (FDR) with LPC; even in the absence of FDR family history of LPC, significantly increased risk for LPC was observed in the presence of at least 1 LPC affected second degree relative (SDR). In the absence of positive FDR and SDR family history for LPC, there was still increased risk for LPC for males with 2 or more third degree relatives with LPC. Early age PC diagnosis in the LPC relative did not appear to affect LPC RR. Higher risks of LPC were associated with the maternal compared to the paternal lineages. Conclusions: Examination of lethal prostate cancer family history (in FDRs through TDRs) may be useful in identifying the cohort of men with prostate cancer most at risk for death from prostate cancer. Focused screening and treatment of this cohort holds potential to decrease the rates of undertreatment of lethal disease while avoiding over diagnosis and overtreatment in inconsequential disease.
Association between expression of insulin resistance (IR) related genes and breast cancer outcome
Authors: A. Gennari, M. Sormani, P. Pronzato, P. Bruzzi, E. Ferrannini, P. Iozzo, M. Roncella, M. Ghilli, V. Mirisola, U. Pfeffer
Journal: Journal of Clinical Oncology (2007)

10597 Background: IR is associated with adverse outcome in breast cancer. IR may affect patient outcome via the insulin and the IGF axis, acting through the tyrosine kinase signaling in enhancing cell proliferation. To date, no study explored the role of insulin- related gene expression in breast cancer progression. The aim of this study was to evaluate the prognostic value of a set of insulin-related genes using published microarray datasets. Methods: IR genes were sorted according to the “insulin sensitivity gene set” previously defined in peripheral tissues of healthy subjects screened for IR by the euglycaemic insulin clamp technique. One-hundred-forty- three genes were used to develop an outcome predictor on a training set of 102 primary breast tumors, randomly selected from 159 patients in the GEO database ( GSE1456 ). The outcome predictor was validated on the remaining 57 patients. Primary outcome measure was relapse free survival (RFS). Univariate non-parametric Mann-Whitney U test was used to identify genes differentially expressed. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median score. Kaplan-Meier curves were used to evaluate the discriminating power of the score. Results: Fourteen genes resulted differentially expressed in the training set: the 8-year RFS was 91% (SE =4%) and 51% (SE = 8%) in the low risk and high risk group, respectively (p &lt; .001). In the validation set, the 8-year RFS was 97% (SE = 3%) and 54% (SE = 10%), respectively (p = .009), supporting the discriminating ability of the score. By multivariate Cox analysis, the prognostic ability of the score was independent of subtype and grade (p &lt; .001). Conclusions: Our data provide the first evidence that expression of insulin related genes can predict outcome, and indicate that the insulin pathway is involved in breast cancer progression. This is particularly important since IR is responsive to lifestyle interventions. We are currently validating the insulin-related score on independent breast cancer microarray datasets. No significant financial relationships to disclose.