tbuckley/cabot-search huggingface dataset:
Hyalinizing trabecular tumors of the thyroid: Clinicopathologic characteristics and treatment outcomes
Authors: S. M. Wiseman, C. Baliski, B. Walker, R. Irvine, D. Anderson, S. Bugis
Journal: Journal of Clinical Oncology (2005)

5601 Background: Hyalinizing Trabecular Tumors (HTT) of the thyroid are uncommon neoplasms believed to be closely related to papillary carcinoma. The objective of this study was to evaluate the clinical and pathologic characteristics and outcomes of HTT treatment. Methods: A prospective clinicopathologic database of 352 sequential thyroid operations carried out over a 4 year period at a tertiary care referral center was retrospectively evaluated to identify all patients with a final pathologic diagnosis of HTT. Clinical data evaluated included patient age and sex and tumor cytology, extent of surgery, tumor size, nodularity, the presence of an associated thyroid carcinoma, and patient outcome. Results: HTT were identified in 3 of 352 thyroid surgical specimens (0.8%).The average age at presentation with HTT was 41 years (range 33 to 49 years). All 3 patients were female. All patients presented with a thyroid nodule and the preoperative fine needle biopsy suggested a ‘follicular neoplasm’ in 2 patients and benign pathology in 1 patient. None of the HTT patients had a history of head and neck irradiation and all 3 underwent hemithyroidectomy. Mean HTT size was 3.4 cm and one case was associated with an incidental 0.7cm focus papillary carcinoma. None of the HTT patients underwent further surgery or other adjuvant therapy. At a mean follow up of 3 years and 5 months no patients developed either recurrent disease or clinical evidence of cancer. Conclusions: HTT are extremely rare neoplasms of the thyroid gland that may present as nodular disease and be associated with papillary carcinoma. We recommend hemithyroidectomy as the initial preferred surgical approach for the management of these clinically indolent tumors No significant financial relationships to disclose.
Temozolomide in resistant or relapsed neuroblastoma
Authors: A. Donfrancesco, G. M. Milano, A. Jenkner, L. de Sio, P. Fidani, I. Ilari, R. Cozza, A. Castellano, C. de Laurentis, C. Dominici
Journal: Journal of Clinical Oncology (2005)

8522 Background: We report the preliminary results of an off-label study investigating the activity of temozolomide (TMZ) in relapsed or resistant neuroblastoma (NB) at dosage of 215 mg/m2/day x 5 days, or 180 mg/m2/day x 5 days in pts with prior autologous bone marrow transplantation (ABMT). Methods: 17 heavily pretreated pts, with stage 3 high risk or stage 4 NB at diagnosis, median age 95 months (range 24 - 203), and resistant or relapsed disease were enrolled. Of 17 pts, 10 had bone marrow involvement and 9 had local relapse. 106 outpatient courses were administered, with a median of 4.8 courses/pt. Bone marrow involvement was evaluated using trephines and multiple aspirates. Immunocytology was performed employing monoclonal antibodies kindly provided by Dr. R.C. Seeger (University of Southern California, Los Angeles, CA). Results: After 2 courses bone marrow responses according to the International Neuroblastoma Response Criteria (INRC) were: 1 VGPR, 1 PR, 3 SDs and 6 PDs. Objective response-rate (CR + PR + MR) was 11.7% (1 CR, 1 MR); SD occurred in 9 pts and PD in 7, with median survival of 7.8 months (range 1 - 41) and median time to progression (TTP) of 3.4 months (range 1 - 20). 1 patient is disease-free (DF) at 37 months and 1 is AWD at 41 months. Hematological toxicity WHO grade 3–4 (mainly thrombocytopenia) was observed in all administered courses, nausea was reported in 3.1%. Conclusions: The results obtained in patients with resistant or relapsed NB, in terms of response and TTP, suggest that TMZ can be potentially useful in a setting of minimal residual marrow disease in high risk NB patients after megatherapy. Combining TMZ with other agents (cis-retinoic acid, molecular targeted agents, biological response modifiers) may further improve outcome in this high risk population. No significant financial relationships to disclose.
A comparative effectiveness analysis of single-agent cytotoxics in triple-negative metastatic breast cancer patients.
Authors: George Dranitsaris, Stefan Glück, Claudio Faria, David Cox, Hope S. Rugo
Journal: Journal of Clinical Oncology (2014)

157 Background: There has been considerable progress in treatments for MBC. However, the identification of optimal cytotoxic agents in patients with triple negative disease (negative for hormone receptors, ER/PR and HER-2) remains a therapeutic challenge. A comparative effectiveness analysis of four cytotoxic agents was conducted in patients with TN MBC. Methods: We retrospectively identified 225 patients treated with single agent eribulin (E=47), capecitabine (C=69), gemcitabine (G=56) or vinorelbine (V=53) in 19 community oncology clinics across the US. Data collection included baseline patient characteristics, performance status, duration of current therapy, growth factor use and all dose limiting toxicities. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was then estimated using the Kaplan-Meier method and Cox proportional hazard modeling adjusted for clustering on the practice site. To control for selection bias that is inherent in observational studies, a propensity score weighted TTF analysis was also conducted. Results: Patients were comparable with respect to age, performance status, duration of disease free survival, presence of comorbidities and hemoglobin level prior to the start of chemotherapy. However, the median lines of therapy for use of C, G, V and E were 2nd, 3rd, 3rd, and 4th, respectively. The median duration of treatment was approximately 2 months with C, G, and E compared to 1.6 months with V. Using eribulin as the reference and adjusting for line of therapy and associated prognostic factors, the propensity score weighted Cox regression analysis did not identify statistically significant differences in TTF: C vs. E: HR = 1.15 (0.75 to 1.76), G vs. E: HR = 0.62 (0.34 to 1.13), V vs. E: HR = 1.0 (0.60 to 1.37). Conclusions: In patients with TN-MBC treated in a community oncology setting, eribulin was utilized in later lines than other agents. However, eribulin demonstrated at least comparable drug activity even when used in more heavily pretreated patients. These findings warrant further analyses in a larger population with an evaluation of biologic heterogeneity.
Gynecologic versus gastrointestinal patients: Preferences (prefs) over time for chemoradiation (chemoXRT) side effects (SE) using visual analog scale (VAS) and time trade-off (TTO).
Authors: C. C. Sun, A. Jhingran, L. M. Ramondetta, P. J. Eifel, C. H. Crane, A. T. Phan, D. Urbauer, M. M. Frumovitz, L. S. Elting, D. C. Bodurka
Journal: Journal of Clinical Oncology (2010)

e19616 Background: ChemoXRT is associated with numerous SE. We assessed SE prefs in GYN and GI pts scheduled for chemoXRT. Methods: Pts were interviewed at 3 timepoints: T1 = prior to initiating chemoXRT; T2 = midway through tx; T3 = 4-6 wks post- tx. Pts evaluated 5 anchor and 16 SE health states (HS) using VAS and 16 SE using TTO. For VAS, HS were rated 0 = worst to 100 = best. TTO asked pts to choose Tx A for 6 wks with SEi (i = SE under consideration) or Tx B with SE= acute nausea/vomiting (NV) for x wks (x < 6 wks). Pts specified timexwhen they felt Tx A=Tx B. Scores were converted to 0.0 =least to 1.0 = most preferred. Data were analyzed by Mann-Whitney and Kruskal-Wallis tests. Results: 110 pts were enrolled. Median age was 53.8 yrs. 42/57 GYN pts had cervical cancer; 40/53 GI pts had distal esophageal/GE junction primaries. All pts received 4-5 wks of external beam XRT and a median of 5 chemo cycles; 74% of GYN pts also had brachytherapy. 98% of GYN pts had cisplatin; 77% of GI pts had 5-FU and platinum±taxane. Overall, VAS and TTO scores increased over time. By VAS, best HS were perfect health, NED, controlled NV, and current health; worst were breakthrough NV, acute/delayed NV, intestinal obstruction, rectovaginal fistula, and death. By TTO, worst HS were breakthrough NV, intestinal obstruction, and rectovaginal fistula. GI pts had consistently higher TTO scores over time vs GYN pts (see Table). GI pts' VAS scores were higher for alopecia (p 0.008), mucositis (p = 0.01) and skin ulcerations (p = 0.01); GYN pts rated diarrhea (p = 0.02), dysuria (p = 0.04) and acute nausea (p = 0.02) higher by VAS. Conclusions: Pt preferences change over the duration of chemoXRT. GYN vs. GI pts have distinctly different preference profiles, which may be due to specific radiation techniques and chemo regimens. TTO scores for GYN vs. GI pts Diarrhea Alopecia Mucositis Skin ulcers Intestinal obstruction BreakthroughNV Time 2 0.74 vs. 0.81 (NS) 0.74 vs. 0.95;p=0.002 0.59 vs. 0.86;p=0.001 0.69 vs.0.86;p=0.04 0.48 vs.0.71;p=0.01 0.57 vs.0.77;p=0.09 Time 3 0.74 vs. 0.85;p=0.01 0.74 vs. 0.96;p<0.001 0.67 vs. 0.83;p=0.02 0.72 vs. 0.87;p=0.05 0.49 vs. 0.81;p<0.001 0.59 vs. 0.080;p=0.03 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck
Survival impact of newly approved therapeutic agents in patients with advanced non-small cell lung cancer (NSCLC): A SEER-Medicare database analysis.
Authors: T. K. Owonikoko, S. S. Ramalingam, M. Behera, J. C. Brandes, N. F. Saba, C. Bhimani, S. Harichand-Herdt, D. M. Shin, F. R. Khuri, C. Ragin
Journal: Journal of Clinical Oncology (2010)

7633 Background: Randomized clinical trials conducted in carefully selected patient populations have led to the approval of novel systemic agents for advanced NSCLC in the last decade. The impact of these agents on survival in the general patient population was assessed. Methods: Patients with stage IIIB/IV NSCLC diagnosed between 1988 and 2005 were eligible; excluded were those with multiple cancers or incomplete survival data. Diagnosis and treatment information was retrieved using the linked SEER-Medicare database. Using the 1988-1994 survival data as a baseline, a temporal survival analysis at time-intervals that mirror widespread adoption of new treatment regimens, (1995-1999-post platinum-doublet, 1999-2003-post second-line therapy, 2004-2005-post-second-/third-line pemetrexed or erlotinib) was performed. Kaplan-Meier method was used to calculate 2- and 5-year survival rates for patient groups at the indicated time periods; statistical difference was tested by log rank test. Cox proportional hazard model adjusted for age, sex, ethnicity and stage was used to estimate the risk of death for each time period relative to baseline risk. Results: There were 146,159 eligible patients; M/F (58%/42%); ethnicity: (Whites-82%; Blacks- 10%; Hispanic: 1.2%; Asians: 2.8%; others-3.3%); stage IIIB/IV (35%/65%); age: 20-64 (12%); 65-69 (21%); 70-79 (45%); 80+ (22%). Temporal analysis showed incremental improvement in the 2-year survival rates (9.17%, 9.97%, 12.83% and 14.5%) as well as reduced risk of death across the time periods- HR and 95% CI: 1995-1998: 0.96, (0.94-0.97, p < 0.0001); 1999-2003: 0.86, (0.85-0.87, p < 0.0001); 2004-2005: 0.79, (0.77-0.8, p < 0.0001). This improvement cut across stage, ethnic and age groups (HR and 95% CI: stage IIIB-: 0.96, [0.93-0.99]; 0.84, [0.82-0.86] and 0.75; [0.73-0.78]; stage IV-: 0.96, [0.94-0.98]; 0.87, [0.86-0.89] and 0.80 [0.73-0.78]). Details of the survival impact for therapeutic agents, age and ethnicity to be provided at the meeting. Conclusions: Survival benefits associated with novel systemic treatment approaches in advanced lung cancer over the last decade (1995-2005) successfully impacted the general U.S. patient population. No significant financial relationships to disclose.
Retinal metastases treated with lapatinib (L) in a young HER2-positive breast cancer patient: Case report
Authors: M. Sarti, O. Pagani, F. Bertoni, S. Longhi, C. Cafaro, R. Graffeo, F. Di Costanzo, A. Goldhirsch
Journal: Journal of Clinical Oncology (2008)

12008 Background: The incidence of ocular metastases (OM) in patients with metastatic breast cancer (BC) is reported to be as high as 30% and is usually associated with short-term fatal outcome and severe impairment of quality of life. OM, predominantly involving the choroids, can be the first sign of systemic spread but are rarely reported, suggesting absent/mild clinical signs and difficult diagnosis. Despite the advances in surgery and radiation therapy, novel therapeutic strategies are eagerly needed to improve the treatment of central nervous system (CNS) metastases, especially of OM, and to reduce side effects. Women with HER2-positive BC are known to have a high incidence of CNS relapse despite effective systemic control with Trastuzumab (T). L is an oral dual tyrosine kinase inhibitor which selectively inhibits both HER1 and HER2 growth factor receptors. The L small molecular size (580 kDa) allows its penetrating the blood-brain barrier and L has been proven to be effective against CNS metastases with an acceptable safety profile and in particular no neurological toxicity. Methods: A 37-year-old woman, shortly after completion of T plus Paclitaxel-Paraplatin chemotherapy for HER2-positive metastatic BC (lung, liver, and bone), complained of rapid decrease of visual acuity with subsequent blindness and local pain which proved to be related to bilateral retinal metastases, without additional intracranial involvement or systemic progression. The patient started L plus capecitabine (X) at recommended doses with significant gastrointestinal toxicity (diarrhoea, gastric pain, dehydration): the dose of X was then reduced to 1,500 mg total daily dose with sustained L at 1,250 mg/daily. Results: visual acuity quickly recovered after treatment start and a complete retinal response was documented after 3 months’ therapy with stable systemic disease. After 6 months’ therapy the patient developed basal skull and trigeminal involvement with no retinal and CNS recurrence or systemic progression. Conclusions: L demonstrated to be a rapidly effective treatment option for this underreported intracranial sanctuary, with a good safety profile as compared to standard current therapies. No significant financial relationships to disclose.
Analysis of antioxidant enzymes combined with the detection of MCL-1 and Bax expressions in acute childhood leukemias
Authors: M. Elbordiny, S. Moawia, I. Elsayed, K. Bassiuony, M. Elshahat
Journal: Journal of Clinical Oncology (2007)

17522 Background: Occurrence and biological characteristics of tumors are related not only to over-proliferation of carcinoma cells but also to decrease of apoptosis. Investigation of apoptosis helps to disclose the biological characteristics of tumors, and seeks new methods of diagnosis and treatment for tumors. In this study, we analyzed the level of some antioxidant enzymes in various leukemic patients including SOD. Methods: To investigate the involvement of apoptosis regulating proteins in acute leukemias, immunocytochemical examination of Mcl-1 and Bax proteins expression was investigated in two groups of patients, one with acute lymphoblastic leukemia (ALL) and the other with acute myeloid leukemia(AML). Moreover, the free radicals utilizing enzymes were sought including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT), in addition to malonaldhyde (MDH), nitric oxide (NO), and glutathione content (GSH). Results: The obtained results showed a significant difference of SOD, GSH-PX, CAT, MDH, NO, and GSH levels in the leukemia patients (AML, ALL) compared to control group (P&lt;0.001 for each comparison). On the other hand, there was a significant difference of SOD, GSH-PX, MDH, NO, and GSH levels in the AML group compared to ALL patients (P&lt;0.001 for each comparison). In AML patients, a significant positive correlation was existed between SOD and GSH-PX (r=0.684, P&lt;0.001) and a negative correlation was existed between catalase and MDH (r=-0.419, P&lt;0.019). Mcl-1 expression was found positive in ten ALL patients out of 31(32.3%) versus 17 out of 31 (54.8%) in AML patients. Concerning Bax reactivity, only seven cases (22.6%) were positive in ALL patients versus 11 cases (35.5%) in AML patients. In ALL patients, a positive correlation was found between Mcl-1 and Bax expressions (r=0.453, P=0.011). Conclusions: Our results collectively reflect remarkable differences between AML and ALL suggesting different mechanisms underlying their formation and their progression. Mcl-1 and Bax expressions relating to the programmed cell death (PCD) or apoptosis in addition to the anti-oxidant status are deregulated mechanisms that contribute in the pathobiology of ALL differently from AML. No significant financial relationships to disclose.
Pulmonary marginal zone lymphoma: A single center experience and review of the SEER database
Authors: A. Stefanovic, D. Morgensztern, T. H. Fong, I. S. Lossos
Journal: Journal of Clinical Oncology (2008)

19508 Background: Pulmonary marginal zone lymphoma (BALT lymphoma) is a rare disease. Few small case series suggest an indolent course with favorable outcome; however, there is limited information on clinical presentation, natural history and treatment of this type of lymphoma. Methods: We conducted a retrospective review of patients with biopsy-proven BALT lymphoma diagnosed between 1994 and 2007 and treated at our institution, and patients from the Surveillance Epidemiology and End Results (SEER) database diagnosed between 1988 and 2003. Results: Twenty-one patients, 11 male and 10 female, with a median age of 57, were identified at our institution. Disease stage was IE (n=10) and IV (n=11), including 7 with extrapulmonary involvement. Initial management included observation (n=4), surgery (n=5), combination chemotherapy (n=7), single-agent rituximab (n=3) and radioimmunotherapy (n=2). Following first- line treatment, complete remission was observed in 10, partial remission in 3, stable disease in 7, and progressive disease in 1 patient. After a median follow-up of 20 months, Kaplan-Meier estimates for progression-free and overall survival at 80 months were 90% and 95%, respectively. We identified 326 patients with BALT lymphoma in the SEER database. This cohort of patients consisted of 59% females and 41% males, with a median age of 68 (30–85+). Fifty-five percent had stage IE, 10% stage IIE, 3% stage IIIE, and 22% stage IV disease. After a median follow-up of 35 months, while median overall survival was 112 months, disease-specific median survival was not reached. At 90 months, disease specific survival was 85% (CI 77–92) with no significant differences in outcome between patients presenting at different stages. Conclusions: Our single institution experience and review of the SEER database, comprising the largest case series of BALT lymphoma reported in the literature, confirm the indolent features and favorable outcome of this rare disease. No significant financial relationships to disclose.
Bicalutamide combination therapy versus castration alone: A combined analysis of historical data
Authors: L. H. Klotz, P. F. Schellhammer, K. J. Carroll
Journal: Journal of Clinical Oncology (2004)

4634 Background: Meta-analyses of randomized trials using flutamide or nilutamide + castration compared with castration alone in D2 prostate cancer have shown a modest overall survival benefit. No direct comparisons have been undertaken of combination therapy using bicalutamide (‘Casodex’) 50 mg with castration alone; here we combine historical data to try to delineate the likely benefit of bicalutamide in this setting. This methodology has been well accepted in other oncology areas: eg in colon cancer, studies comparing the efficacy of 5-fluorouracil (5-FU) + leucovorin to 5-FU alone, and 5-FU + leucovorin to capecitabine, were integrated on the principle that equivalent groups were being compared in otherwise disparate studies (Stat Med 2003;22:239–64). This analysis resulted in FDA approval for capecitabine based on this approach. Methods: A double-blind, randomized, multicenter trial comparing bicalutamide and flutamide combination therapy (Urology 1997;50:330–6) was combined with the Prostate Cancer Trialists' Collaborative Group (PCTCG) meta-analysis for flutamide + castration vs castration alone (Lancet 2000;355:1491–8). The HR was estimated by multiplying the combination therapy HR for bicalutamide vs flutamide by the HR for flutamide combination therapy vs castration alone. The statistical uncertainty was calculated as the sum of the variances in the comparison of bicalutamide vs flutamide combination therapy, and the effect of flutamide in the PCTCG meta-analysis. The key assumption is that the effect of flutamide in both populations was the same. The lack of heterogeneity in the effect of flutamide in the PCTCG analysis supports this assumption. Results: The analysis showed that there is a 98.5% probability that bicalutamide, as combination therapy with an LHRHa, provides a survival advantage over castration alone. The estimated HR is 0.80 (95% CI 0.66, 0.98) (ie 20% risk reduction). Conclusions: There is a high probability that bicalutamide (given once daily) + castration provides a survival advantage over castration alone. The estimated reduction in risk of death is 20%. ‘Casodex’ is a trademark of the AstraZeneca group of companies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca